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1.  Thrombus-like Tumor of Renal Cell Carcinoma Mimicking Transitional Cell Carcinoma of Kidney: A Case Report 
Urology Case Reports  2016;10:26-29.
Renal cell carcinoma (RCC) is the most common malignancy of the kidney. It is not commonly form tumor thrombus in the ureter or renal pelvis. A 29-year-old woman presented with asymptomatic gross hematuria. Contrast CT study revealed a tumor suspected to be a Transitional Cell Carcinoma (TCC). However, tumor thrombus was found in the renal pelvis and ureter. We performed Nephroureterectomy, bladder cuff excision, and lymph node dissection, and the tumor was diagnosed histopathologically as RCC. We report a very rare case of thrombus-like tumor of renal cell carcinoma mimicking transitional cell carcinoma of kidney.
PMCID: PMC5122699  PMID: 27896135
Upper tract urothelial carcinoma; Renal cell carcinoma; Uteral invasion; Thrombus-like tumor
2.  AB122. Changing from open to laparoscopic surgery and medium-term prognosis of renal cell carcinoma patients with venous tumor thrombus: a single center study of 276 cases 
Translational Andrology and Urology  2015;4(Suppl 1):AB122.
To review retrospectively the clinical information of patients with renal cell carcinoma (RCC) and venous tumor thrombus, and to evaluate the changing from open to laparoscopic surgery and medium-term prognosis of these patients.
From Jan 2000 to Dec 2014, 276 patients were treated with renal cell carcinoma and venous tumor thrombus at our institute. It was analyzed for their clinical and perioperative data and follow-up information.
There were 133 and 143 patients with renal vein (RV) and inferior vena cava (IVC) tumor thrombus respectively, which include 84 with IVC level I, 38 with IVC level II and 21 with IVC level III. There were several steps for the changing from open to laparoscopic surgery for RCC patients with venous tumor thrombus. (I) Traditional open surgery: before 2012, open surgery was routinely done for such kind of patients. For those with large tumor and advanced tumor thrombus, the renal artery may be embolized preoperatively, which could ease the renal dissection and the artery control during surgery. There were 52 patients with advanced tumor thrombus above the hepatic vein in our study, who underwent cardiopulmonary bypass (CPB) assisted surgery without major complication. (II) Retroperitoneal laparoscopic surgery first and then transperitoneal open surgery: from 2012, we introduced laparoscopic techniques into the operation for these patients. For those with IVC tumor thrombus, we could effectively combine the advantages of the retroperitoneal laparoscopic procedure in rapid renal pedicle control and the open transperitoneal procedure in IVC tumor thrombectomy. Compared with the traditional open surgery group, the combined surgery group showed shorter operation time (225 vs. 300 min), less blood loss (150 vs. 625 mL) and shorter hospitalization time (7 vs. 11 days) (all P<0.05). (III) Combined retroperitoneal and transperitoneal pure laparoscopic procedure: from 2013, we had completed six cases of pure laparoscopic surgery with this combined pathway for RCC patients with early IVC tumor thrombus (level I and level II, below hepatic vein), which could take advantages of both laparoscopic pathways and minimize the injury to patients. The median follow-up time was 52 months for all patients (range, 6-138 months) with a follow-up rate of 81.2% (224/276). The median survival time was 58 months and the 5-yr overall survival rate was 48.7% for all patients. There was no significant difference between the prognosis of patients with RV and IVC tumor thrombus (P=0.117), while patients with early tumor thrombus (below hepatic vein) showed significantly improved survival than those with advanced tumor thrombus (above hepatic vein) (P=0.011).
Because of the complexity and difficulty of these surgical procedures, we routinely did traditional open surgery for patients with RCC and venous tumor thrombus before 2012. With the development of laparoscopic techniques in recent years, the operation for these patients turned to be minimally invasive-pure laparoscoic for tumor thrombus below hepatic vein, with good tumor control and promising middle-term prognosis.
PMCID: PMC4708829
Renal cell carcinoma (RCC); venous tumor thrombus; surgery strategy; prognosis
3.  Concurrent occurrence of renal cell carcinoma with rhabdoid features in a married couple: a case report 
BMC Research Notes  2015;8:3.
Renal cell carcinoma (RCC) with rhabdoid features is a rare histology and exhibits clinically aggressive behavior. We report a case of a married couple in whom RCC with rhabdoid features concurrently occurred. The rarity of this event suggests that environmental factors may contribute to the etiology of RCC with rhabdoid features.
Case presentation
A 76-year-old Japanese woman was diagnosed with a hypervascular mass in the right kidney and tumor thrombus extending into the right atrium by enhanced computed tomography (CT). She underwent radical nephrectomy and tumor thrombectomy following systemic therapy with the tyrosine kinase inhibitor sunitinib. The histological evaluation denoted clear cell RCC with rhabdoid features. The patient died of cancer 12 months postoperatively. A 76-year-old man, her husband, presented with gross hematuria 2 weeks after his wife had undergone surgery. He had a long history of asbestos exposure. An abdominal CT scan revealed a hypervascular mass in the right kidney and tumor thrombus extending into the inferior vena cava. He also underwent radical nephrectomy and tumor thrombectomy. The histological evaluation also showed clear cell RCC with rhabdoid features. Bone metastasis occurred 12 months postoperatively, but he died of an unrelated cause 18 months after surgery.
Concurrent occurrence of RCC with rhabdoid features may not to be coincidental. Although further studies are warranted, asbestos exposure may contribute to the etiology of clear cell RCC with rhabdoid features.
PMCID: PMC4302605  PMID: 25588411
Renal cell carcinoma; Rhabdoid features; Married couple; Asbestos
4.  Cardiopulmonary bypass-assisted surgery for the treatment of Xp11.2 translocation/TFE3 gene fusion renal cell carcinoma with a tumor thrombus within the inferior vena cava: A case report 
Oncology Letters  2015;10(6):3532-3534.
Renal cell carcinoma (RCC) accounts for 85–90% of kidney cancers, which in turn account for 2–3% of all malignant tumors in adults. Xp11.2 translocation/TFE3 gene fusion RCC is currently classified as a distinct type of RCC. RCC is capable of invading the renal vein and inferior vena cava to form a tumor thrombus. The incidence of RCC with tumor thrombi within the renal vein or inferior vena cava is 7–10% in China. In the present case report, the patient underwent radical resection of the renal tumor and removal of the tumor thrombus, assisted by cardiopulmonary bypass, for the treatment of Xp11.2 translocation/TFE3 gene fusion RCC. The patient was followed-up for 12 months subsequent to treatment. The patient's renal function remained within the normal range, and computed tomography examination revealed no evidence of disease recurrence or metastases. The present case report aimed to provide a reference for the development of guidelines for the diagnosis and treatment of Xp11.2 translocation/TFE3 gene fusion RCC.
PMCID: PMC4665330  PMID: 26788164
cardiopulmonary bypass; Xp11.2 translocation/TFE3 gene fusion; tumor thrombus; surgery; diagnostic
5.  Increased risk of preoperative venous thromboembolism in patients with renal cell carcinoma and tumor thrombus 
The clinical impact of a tumor thrombus in renal cell carcinoma (RCC) patients awaiting radical nephrectomy and thrombectomy is unknown.
To determine the incidence of venous thromboembolism (VTE) in RCC patients with tumor thrombus prior to nephrectomy.
Patients and methods
We conducted a retrospective cohort study including all late-stage (stage 3–4 excluding T1–2 N0M0) RCC patients who underwent radical nephrectomy at our institution between 1 January 2005 and 1 July 2012. Tumor thrombus was defined as the presence of an intraluminal filling defect in the renal vein, hepatic vein, portal vein, or inferior vena cava, directly extending from a renal mass detected on computed tomography.
A total of 176 patients were included in the study. Fifty-three (30.1%) patients had tumor thrombus diagnosed on imaging Three patients with tumor thrombus (5.7%; 95% confidence interval [CI] 1.4–16.8) developed a VTE while awaiting radical nephrectomy, whereas none (0%; 95% CI 0–2.9) of the patients without a tumor thrombus had an event (P = 0.026). All three events were deep vein thrombosis. Times from tumor thrombus diagnosis to VTE were 5, 15 and 21 days.
Tumor thrombus on imaging is a frequent finding among RCC patients awaiting nephrectomy. The presence of tumor thrombus in these patients increases the incidence of preoperative VTE.
PMCID: PMC4238732  PMID: 24283651
neoplasm; nephrectomy; renal cell carcinoma; thrombosis; venous thromboembolism
6.  Laparoscopic radical nephrectomy with inferior vena cava thrombectomy: highlight of key surgical steps 
Vascular involvement in the form of renal vein (RV) or inferior vena cava (IVC) thrombus can be seen in 4-10% of patients presented with RCC. In patients without presence of metastasis, surgical treatment in the form of radical nephrectomy remains the treatment of choice with 5-year survival rates of 45-70%. Open surgery is still the first treatment option of choice at the moment for RCC patients with IVC thrombus.
Materials and Methods:
In our study, we are reporting a case of patient with RCC and level I IVC thrombus treated with laparoscopy. Our patient is a 72 years old man with underlying co-morbidity of hypertension and chronic kidney disease (CKD) presented with right-sided RCC. The CT scan done showed a large right renal upper pole tumor measuring 8.4x5.2cm with level I IVC thrombus (Figure-1). There were no regional lymphadenopathy and the staging scans were negative.
The operative time was 124 minutes and blood loss was minimal. The patient was progressed to diet on POD 1 with bowel movement on POD 2. There was no significant change in the pre and post-operative glomerular filtration rate (GFR). The surgical drain was removed on POD2. The patient was discharged well on POD 5. There were no perioperative complications. The pathology was pT3bN0M0 Fuhrman grade II clear cell RCC.
As a conclusion, laparoscopic radical nephrectomy and IVC thrombectomy is a complex and technically demanding surgery. With advancement of surgical skills as well as technology, more cases of minimally invasive laparoscopic radical nephrectomy and IVC thrombectomy can performed to improve the perioperative outcomes of carefully selected patients in a high volume center.
PMCID: PMC5006791  PMID: 27564306
7.  Wilms tumor with intravascular tumor thrombus 
Translational Pediatrics  2014;3(1):29-33.
Wilms tumor (WT) is one of the most common solid tumors in children. It is the second most common extracranial solid tumor after neuroblastoma. WT has a strong tendency to invade blood vessels in the form of tumor thrombus, into the renal veins, and inferior vena cava and even into the right atrium. Extension of tumor thrombus along to the renal vein into the inferior vena cava occurs in 4-10% of all patients. Tumor thrombus extending to the right atrium is less reported as 0.7-1%. WT with renal vein thrombus has been reported to be more common in the right kidney because of the shorter right renal vein. Most patients with tumor thrombus are asymptomatic and diagnosis is only made on imaging investigations. Several imaging modalities including computed tomography (CT), magnetic resonance imaging (MRI) and Doppler ultrasonography (USG) can demonstrate intravascular tumor thrombus before surgery. In addition to CT and MRI, Doppler USG is reliable in demonstrating the presence and extent of inferior vena cava tumor thrombus. The management of WT with tumor thrombus is determined by multiple factors such as extent of tumor thrombus, chemotherapy response of the tumor. Now, it is generally recommended to use preoperative chemotherapy to a patient presenting with intravascular tumor thrombus. This approach is helpful to decrease the extent of the vascular thrombus which facilitates surgical excision. Most intracaval and intraatrial thrombi in WT show a response to chemotherapy. Neoadjuvant chemotherapy causes tumor regression in nearly half of the patients. Most of them can be managed without the need for cardiac bypass surgery. The decision of initial surgery or preoperative chemotherapy should be carefully determined on every case. Primary surgery would only be indicated in a patient who is unstable because of thrombus that might dislodge and cause acute symptoms. Presence of tumor thrombus in WT needs for multidisciplinary care including pediatric oncologists, pediatric surgeons, and pediatric cardiac surgeons.
PMCID: PMC4728852  PMID: 26835320
Wilms tumor (WT); intravascular extension; tumor thrombus
8.  Prognostic benefit of surgical management in renal cell carcinoma patients with thrombus extending to the renal vein and inferior vena cava: 17-year experience at a single center 
BMC Urology  2013;13:47.
Management of renal cell carcinoma (RCC) with tumor thrombus extending to the renal vein and inferior vena cava (IVC) is challenging. The aim of this study was to evaluate the benefit of surgical management in such patients.
From February 1995 to February 2013, 520 patients were treated for RCC at Hirosaki University Hospital, Hirosaki, Japan. The RCC patients with tumor thrombus extending to the renal vein (n = 42) and IVC (n = 43) were included in this study. The records of these 85 patients were retrospectively reviewed to assess the relevant clinical and pathological variables and survival. Prognostic factors were identified by multivariate analysis. The benefit of surgical management was evaluated using propensity score matching to compare overall survival between patients who received surgical management and those who did not.
RCC was confirmed by pathological examination of surgical or biopsy specimens in 74 of the 85 patients (87%). Sixty-five patients (76%) received surgical management (radical nephrectomy with thrombectomy). Distant metastasis was identified in 45 patients (53%). The proportion of patients with tumor thrombus level 0 (renal vein only), I, II, III, and IV was 49%, 13%, 18%, 14%, and 5%, respectively. The estimated 5-year overall survival rate was 70% in patients with thrombus extending to the renal vein and 23% in patients with thrombus extending to the IVC. Multivariate analysis identified thrombus extending to the IVC, presence of distant metastasis, surgical management, serum albumin concentration, serum choline esterase concentration, neutrophil-lymphocyte ratio, and Carlson comorbidity index as independent prognostic factors. In propensity score-matched patients, overall survival was significantly longer in those who received surgical management than those who did not.
Surgical management may improve the prognosis of RCC patients with thrombus extending to the renal vein and IVC.
PMCID: PMC3852853  PMID: 24125174
Renal cell carcinoma; Radical nephrectomy with thrombectomy; Tumor thrombus; Prognostic factors
9.  Contralateral ureteral metastasis 4 years after radical nephrectomy 
Metastasis of renal cell carcinoma to the contralateral ureter is extremely rare. To date, only 50 cases of metastatic RCC to the ureter have been reported, among whom 6 cases occur at the contralateral site. We herein report a rare case of metastatic RCC in the contralateral ureter 4 years after radical nephrectomy.
Presentation of case
A 74-year-old man presented with gross, painless hematuria for one month. Computed tomography scan confirmed that a 1.5 cm × 0.5 cm tumor occurred in the contralateral distal ureter. A 3.5 cm segment of ureter was resected and a uretero-vesical anastomosis with psoas hitch was accomplished.
The reappearance of hematuria after radical nephrectomy is the most common manifestation of the metastasis to the bladder or ureter. The mechanism of metastasis is not clear. In pathology, vimentin and cytokeratins might help to differentiate between metastatic clear cell renal cell carcinoma and clear cell transitional cell carcinoma.
Metastasis of renal cell carcinoma to the contralateral ureter is rare. Early recognition is extremely important in protecting the remaining renal function and prolonging life-expectancy for post-nephrectomy patients. Complete metastectomy suitable anastomosis have been shown to improve survival.
PMCID: PMC3267242  PMID: 22288039
Renal cell carcinoma; Ureteral metastasis
10.  Impact of miR-21, miR-126 and miR-221 as Prognostic Factors of Clear Cell Renal Cell Carcinoma with Tumor Thrombus of the Inferior Vena Cava 
PLoS ONE  2014;9(10):e109877.
Clear cell renal cell carcinoma (ccRCC) characterized by a tumor thrombus (TT) extending into the inferior vena cava (IVC) generally indicates poor prognosis. Nevertheless, the risk for tumor recurrence after nephrectomy and thrombectomy varies. An applicable and accurate prediction system to select ccRCC patients with TT of the IVC (ccRCC/TT) at high risk after nephrectomy is urgently needed, but has not been established up to now. To our knowledge, a possible role of microRNAs (miRs) for the development of ccRCC/TT or their impact as prognostic markers in ccRCC/TT has not been explored yet. Therefore, we analyzed the expression of the previously described onco-miRs miR-200c, miR-210, miR-126, miR-221, let-7b, miR-21, miR-143 and miR-141 in a study collective of 74 ccRCC patients. Using the expression profiles of these eight miRs we developed classification systems that accurately differentiate ccRCC from non-cancerous renal tissue and ccRCC/TT from tumors without TT. In the subgroup of 37 ccRCC/TT cases we found that miR-21, miR-126, and miR-221 predicted cancer related death (CRD) accurately and independently from other clinico-pathological features. Furthermore, a combined risk score based on the expression of miR-21, miR-126 and miR-221 was developed and showed high sensitivity and specificity to predict cancer specific survival (CSS) in ccRCC/TT. Using the combined risk score we were able to classify ccRCC/TT patients correctly into high and low risk cases. The risk stratification by the combined risk score (CRS) will benefit from further cohort validation and might have potential for clinical application as a molecular prediction system to identify high- risk ccRCC/TT patients.
PMCID: PMC4184907  PMID: 25279769
11.  AB118. Feasibility and safety evaluation of pure laparoscopic radical nephrectomy and thrombectomy for renal tumor patients with venous tumor thrombus 
Translational Andrology and Urology  2015;4(Suppl 1):AB118.
To evaluate the feasibility and safety of pure laparoscopic radical nephrectomy and thrombectomy for renal tumor patients with venous tumor thrombus.
From Jan 2013 to Dec 2014, records of patients with renal tumor and venous thrombus treated in our institute were retrospectively reviewed. Thirteen patients underwent pure laparoscopic radical nephrectomy and thrombectomy, including seven patients with renal vein (RV) thrombus and six patients with inferior vena cava (IVC) thrombus. Retroperitoneal approach was undertaken for RV thrombus patients, while transperitoneal approach or combined retroperitoneal and transperitoneal approach for IVC thrombus patients. During the combined approach surgery, renal artery and lumbar vein were controlled through retroperitoneal approach, and the thrombectomy procedure was completed through transperitoneal approach.
There were nine male patients and four female patients. All patients ranged from 30 to 78 years old (median, 55 years old). Seven patients were diagnosed by routine medical examination, while six patients had clinical symptoms, including four with gross hematuria and two with flank pain. All patients underwent operations successfully. Operation time ranged from 84 to 456 minutes (median 195 minutes). The blood loss ranged from 50 to 150 mL (median, 50 mL) for RV tumor thrombus patients, and 100 to 2,500 mL (median, 325 mL) for IVC tumor thrombus patients. All patients recovered well after surgery without major complications. With the postoperative pathological examination, the average tumor maximum diameter was 7.9±2.5 cm. Eleven cases of clear cell renal cell carcinoma, one case of chromophobe renal cell carcinoma and one case of renal metastatic osteosarcoma were showed in our study. Median follow-up time was 13 months (2-22 months). No decease was observed at the last follow-up. Three patients experienced distant metastasis after surgery, including two patients with multiple pulmonary metastases and one patient with lumbar vertebral metastasis.
Pure laparoscopic radical nephrectomy and thrombectomy is feasible and safe, with promising oncological prognosis. Combined retroperitoneal and transperitoneal procedures can take both the advantages of these two approaches and simplify operative manipulations.
PMCID: PMC4708694
Renal tumor; venous tumor thrombus; laparoscopic surgery
12.  Tumor thrombus of inferior vena cava in patients with renal cell carcinoma – clinical and oncological outcome of 50 patients after surgery 
BMC Research Notes  2012;5:264.
To evaluate oncological and clinical outcome in patients with renal cell carcinoma (RCC) and tumor thrombus involving inferior vena cava (IVC) treated with nephrectomy and thrombectomy.
We identified 50 patients with a median age of 65 years, who underwent radical surgical treatment for RCC and tumor thrombus of the IVC between 1997 and 2010. The charts were reviewed for pathological and surgical parameters, as well as complications and oncological outcome.
The median follow-up was 26 months. In 21 patients (42%) distant metastases were already present at the time of surgery. All patients underwent radical nephrectomy, thrombectomy and lymph node dissection through a flank (15 patients/30%), thoracoabdominal (14 patients/28%) or midline abdominal approach (21 patients/42%), depending upon surgeon preference and upon the characteristics of tumor and associated thrombus. Extracorporal circulation with cardiopulmonary bypass (CPB) was performed in 10 patients (20%) with supradiaphragmal thrombus of IVC. Cancer-specific survival for the whole cohort at 5 years was 33.1%. Survival for the patients without distant metastasis at 5 years was 50.7%, whereas survival rate in the metastatic group at 5 years was 7.4%. Median survival of patients with metastatic disease was 16.4 months.
On multivariate analysis lymph node invasion, distant metastasis and grading were independent prognostic factors. There was no statistically significant influence of level of the tumor thrombus on survival rate. Indeed, patients with supradiaphragmal tumor thrombus (n = 10) even had a better outcome (overall survival at 5 years of 58.33%) than the entire cohort.
An aggressive surgical approach is the most effective therapeutic option in patients with RCC and any level of tumor thrombus and offers a reasonable longterm survival. Due to good clinical and oncological outcome we prefer the use of CPB with extracorporal circulation in patients with supradiaphragmal tumor thrombus. Cytoreductive surgery appears to be beneficial for patients with metastatic disease, especially when consecutive therapy is performed. Although sample size of our study cohort is limited consistent with some other studies lymph node invasion, distant metastasis and grading seem to have prognostic value.
PMCID: PMC3427529  PMID: 22658129
Renal cell carcinoma; Inferior vena cava; Thrombectomy; Tumor thrombus
13.  Clinical and histopathological effects of presurgical treatment with sunitinib for renal cell carcinoma with inferior vena cava tumor thrombus at a single institution 
Anti-Cancer Drugs  2016;27(10):1038-1043.
To evaluate the clinical and histopathological effects of presurgical treatment with sunitinib on inferior vena cava (IVC) tumor thrombus. Between 2010 and 2014, we treated seven patients with renal cell carcinoma and IVC tumor thrombus presurgically with sunitinib. We retrospectively evaluated primitive tumor size, the level of tumor thrombus according to Novick’s classification, its distance above the renal vein, thrombus diameter at its widest segment, and histopathological change after sunitinib treatment. Three patients were diagnosed histologically. Percutaneous biopsy of the renal mass before sunitinib treatment was performed in two patients. One patient was diagnosed after sunitinib treatment following nephrectomy. The primitive tumors shrank upon sunitinib therapy in four cases; however, although the caval thrombus was downstaged (from level II to I) in one patient, the level of caval thrombus did not change in five patients and increased in one patient (from level III to IV). We evaluated the histopathological effects in two patients. In one patient, the IVC tumor thrombus was mostly replaced with necrotic tissue, but its thrombus level was not downstaged. In the other patient, the IVC tumor thrombus was downstaged, but tumor thrombus was not replaced with necrotic tissue and viable tumor cells remained. Presurgical treatment with sunitinib for renal cell carcinoma with IVC tumor thrombus appears to have limited effect on IVC tumor thrombus, in contrast to its effects on primitive tumor shrinkage. In the absence of evidence of presurgical benefits from prospective studies, this treatment may not be systematically advisable.
PMCID: PMC5049971  PMID: 27557138
inferior vena cava thrombus; molecular-targeted therapy; presurgical treatment; renal cell carcinoma; sunitinib
14.  AB065. Totally retroperitoneal laparoscopic radical nephrectomy with inferior vena cava thrombectomy (Mayo 0-3) 
Translational Andrology and Urology  2015;4(Suppl 1):AB065.
Background and Objective
Management of renal cell carcinoma (RCC) with tumor thrombus extending to the renal vein and inferior vena cava (IVC) is challenging. The aim of this study was to evaluate the benefit of totally retroperitoneal laparoscopic radical nephrectomy with inferior vena cava thrombectomy in such patients.
Patients and Methods
From July 2014 to May 2015, 12 patients underwent laparoscopic radical nephrectomy for renal cell cancer combined with tumor thrombus of the inferior vena cava. Thrombus extension classified by the Mayo Clinic and the 2009 TNM classifications, complications, postoperative management, and survival results were analyzed. The surgeries were performed by retroperitoneal approach totally. For substantial level I-III involvement, complete caval isolation, including laparoscopic control of infra-renal and supra-renal IVC, contra-lateral renal vein and lumbar veins was performed. Following thrombus extraction, the cavotomy was repaired with 4-0 prolene suture on RB-1 needle.
Four patients had level 0, two patients had level I, five had level II, and one had level III thrombi according to the Mayo Clinic staging, and 11 were T3c and one was T4 according to the 2009 TNM classifications. Totally retroperitoneal laparoscopic approach was performed in patients with stage 0 to 3 thrombi. There was no intraoperative mortality and open conversion. The median follow-up interval was 8.6 months.
Renal cell cancer complicated with tumor thrombus without metastasis can be curable by performing a complete resection. The thrombus level determines the surgical approach and method. Our results confirm that Mayo level 0-3 caval vein tumor thrombus can be safely surgically treated by totally retroperitoneal laparotomy.
PMCID: PMC4708760
Renal cell carcinoma (RCC); radical nephrectomy with thrombectomy; tumor thrombus
15.  Cutaneous metastasis of renal cell carcinoma: a report of two cases 
Cutaneous metastasis of renal cell carcinoma (RCC) is very rare. The author herein report two cases of RCC with cutaneous metastasis. Case 1: is a 75-year-old man with right lumbago. Imaging modalities including CT and MRI revealed a right renal tumor. Nephrectomy was performed. Pathological diagnosis of the renal tumor was RCC of clear cell type (Fuhrman's grade II). He denied follow-up. Nine years later, he (at the age of 84 years), a neck skin tumor emerged. Clinical diagnosis was hemangioma. Imaging modalities including CT and MRI showed several tumors in both lungs. The resection of the neck tumor was performed. The tumor was composed of clear cell type arranged in a trabecular pattern. Immunohistochemically, the tumor cells were positive for pancytokeratins, cytokeratin 18, CD10, Ki-67 (labeling=13%), but negative for CD34, factor-VIII-related antigen, CEA, EMA, melanosome (HMB45), S100 protein, p53, and HepPar-1. Metastatic RCC was diagnosed. Despite interferon therapy, he died of 6 months after the second admission. Case 2 is a 66-year-old man with gross hematuria. Imaging modalities revealed left renal tumor. A nephrectomy was performed. The pathological diagnosis was RCC of clear cell type (grade II). The tumor was invasive into the renal pelvis. He was treated by chemoradiation, but metastases of lungs, skin (thigh), and lib emerged, and died of cachexia 9 months after the admission. Necropsy of the skin tumor was performed. The skin tumor was composed of clear cells arranged in a trabecular pattern. Immunohistochemically, the tumor cells were positive for pancytokeratins (AE1/3, CAM5.2), CD10, p53, and Ki-67 (labeling=20%), but negative for CD34, factor-VIII-related antigen, CEA, melanosome (HMB45), S100 protein, and HepPar-1. A diagnosis of RCC (grade II) was diagnosed.
PMCID: PMC3294234  PMID: 22400081
Skin; metastasis; renal cell carcinoma; immunohistochemistry
16.  Surgical resection of recurrent inferior vena cava tumor following radical nephrectomy for renal cell carcinoma: A case report 
Oncology Letters  2015;10(1):111-114.
Late recurrence is a known characteristic of the biological behavior of renal cell carcinoma (RCC) following radical nephrectomy. However, the development of recurrent inferior vena cava (IVC) tumors following radical nephrectomy for RCC is a rare event, and surgical resection of recurrent IVC tumors is a challenge for urologists. The present study reports the case of a patient with a local recurrent tumor in the IVC following a right radical nephrectomy 4 years previously for RCC. The patient was referred to the Department of Urology, First Affiliated Hospital of Anhui Medical University, due to bilateral lower extremity edema, and magnetic resonance imaging showed an intraluminal tumor thrombus in the IVC. Therefore, a thrombectomy and partial IVC resection with defect reconstruction were performed successfully. The results of follow-up for 72 months showed that there were no signs of recurrence as local or distant metastasis. This case of local recurrence in the IVC highlights that active long-term surveillance for RCC patients of all stages is important for the early diagnosis of tumor recurrence, which improves the potential resectability.
PMCID: PMC4486889  PMID: 26170985
recurrence; inferior vena cava; renal cell carcinoma; radical nephrectomy
17.  Stereotactic radiation therapy of renal cancer inferior vena cava tumor thrombus 
Cancer Biology & Therapy  2015;16(5):657-661.
Renal Cell Carcinoma (RCC) is a common malignancy world-wide that is rising in incidence. Up to 10% of RCC patients present with inferior vena cava (IVC) tumor thrombus (IVC-TT). Although surgery is the only treatment with proven efficacy for IVC-TT, the surgical management of advanced (level III and IV) IVC-TT is difficult with high morbidity and mortality, and offers a poor survival outcome. Currently, there are no treatment options in the setting of recurrent or unresectable RCC IVC-TT. Even though RCC may be resistant to conventionally fractionated radiation therapy, hypofractionated radiation has shown excellent control rates for both primary and metastatic RCC. We report our experience treating 2 RCC patients with Level IV IVC-TT —one recurrent and the other unresectable—with stereotactic ablative radiation therapy (SABR). The first patient is a 75-year-old gentleman with a level IV RCC IVC-TT who presented 9 months after his radical nephrectomy and thrombectomy with a growing level IV IVC-TT that became refractory to 4 targeted agents. He received SABR of 50Gy in 5 fractions and at 2-year follow-up is doing well with a significant decrease in the enhancement and size of the IVC-TT. The second patient is an 83-year-old gentleman who presented with metastatic RCC and level IV IVC-TT but was not a surgical candidate. After progression on temsirolimus, he received SABR of 36Gy in 4 fractions to his IVC-TT and survived 18 months post-SABR. Both patients improved symptomatically and did not experience any acute or late treatment-related toxicity. Their survival of 24 months and 18 months are comparable to the reported median survival of 20 months in patients with level IV IVC-TT that underwent surgical resection. Therefore, SABR can be a potentially safe treatment option in the unresectable setting for RCC patients with IVC-TT and should be further evaluated in prospective trials.
PMCID: PMC4622024  PMID: 25800036
renal cell carcinoma; radiosurgery; stereotactic body radiotherapy
18.  Early occlusion control of the intrapericardial inferior vena cava under femoral–femoral extracorporeal circulation using a technique to prevent pulmonary embolism during nephrectomy for renal cell carcinoma with tumor thrombus: two case reports 
BMC Research Notes  2014;7:683.
Renal cell carcinoma with tumor thrombus extension into the inferior vena cava occurs in approximately 5% of cases. Despite such situations, an aggressive surgical approach is recommended. However, intraoperative prevention of pulmonary embolism by a fragmended tumor thrombus is necessary. To prevent pulmonary embolism, placement of a temporary suprarenal filter has been attempted, however, the precise placement of a temporary filter between the level of the hepatic vein and right atrium is not always easy because of its migration, tilting, and strut fracture. Here we report a method for early occlusion control of the intrapericardial inferior vena cava to prevent pulmonary embolism during nephrectomy in level II or III renal cell carcinoma tumor thrombus.
Case presentation
Our first case was a 37-year-old Japanese man with left renal cell carcinoma extending into the inferior vena cava below the main hepatic vein (level II) and our second was a 75-year-old Japanese man with right renal cell carcinoma extending into the retrohepatic inferior vena cava at the main hepatic vein (level III). En block resection of the kidney and the tumor thrombus was performed with the aid of partial extracorporeal circulation; the postoperative course of both patients was uneventful.
Control of intrapericardial inferior vena cava is a feasible method to prevent pulmonary embolism.
PMCID: PMC4190328  PMID: 25270542
Intrapericardial inferior vena cava; Renal cell carcinoma; Tumor thrombus; Pulmonary embolism
19.  AB106. Differential regulation of LncRNA-SARCC suppresses VHL-mutant RCC cell proliferation yet promotes VHL-normal RCC cell proliferation via modulating androgen receptor/HIF-2α/C-MYC axis under hypoxia 
Translational Andrology and Urology  2016;5(Suppl 1):AB106.
It is well established that hypoxia contributes to tumor progression in a HIF-2α-dependent manner in renal cell carcinoma (RCC), yet the role of LncRNAs involved in hypoxia-mediated RCC progression remains unclear. Here we demonstrate that LncRNA-SARCC is differentially regulated by hypoxia in a VHL-dependent manner both in tissue culture and in human RCC clinical samples. LncRNA-SARCC can suppress hypoxic cell cycle progression in the VHL-mutant RCC cells while derepress it in the VHL-restored RCC cells. Mechanism dissection reveals that LncRNA-SARCC can post-transcriptionally regulate androgen receptor (AR) by physically binding and destabilizing AR protein to suppress AR/HIF-2α/C-MYC signals. In return, HIF-2α can transcriptionally regulate the LncRNA-SARCC expression via binding to hypoxia responsive elements (HREs) on the promoter of LncRNA-SARCC. The negative feedback modulation between LncRNA-SARCC/AR complex and HIF-2α signaling may then lead to differentially modulate RCC progression in a VHL-dependent manner. Together, these results may provide us a new therapeutic approach via targeting this newly identified signal from LncRNA-SARCC to AR-mediated HIF-2α/C-MYC signals against RCC progression.
Human samples—surgical specimens from human ccRCC tissues were obtained from 16 patients in the Department of Urology, Shanghai Tenth People’s Hospital, Tongji Medical School (Shanghai, China), freshly frozen in liquid nitrogen and stored at −80 °C until use. OCT-embedded blocks were sectioned until cut planes were >70% tumor. Sections were collected for DNA, RNA, and protein extraction. Samples were cataloged, clinical information on cases was obtained through chart review, and patient identifiers were removed before analysis. Informed consent was obtained from patients and the study was approved by the Institutional Review Board of Tongji Medical College. Immunohistochemistry—immunohistochemical staining was performed as previously described [40], with antibodies specific for HIF-1α, HIF-2α, C-MYC, Ki-67, AR (Abcam Inc., Cambridge, MA, USA; 1:200 dilution) and CAIX (Santa Cruz Biotechnology, Santa Cruz, CA, USA; 1:200 dilution). The reactivity degree was assessed by at least two pathologists without knowledge of the clinicopathological features of tumors. The degree of positivity was initially classified according to the percentage of positive tumor cells as the following: (−) >5% cells positive, (1+) 6–25% cells positive, (2+) 26–50% cells positive, and (3+) >50% cells positive. For AR, HIF-1α, HIF-2α, C-MYC, Ki-67 and CAIX, samples were scored as negative/weak, intermediate, or strong. Only cells with clear tumor cell morphology were scored. Cell culture and transfection—the human VHL-mut RCC cell lines SW839 (AR positive), OSRC-2 (AR positive), A498 (AR negative), 769-P (AR negative), 786-O (AR negative), and the human VHL-wt RCC cell lines Caki-1 (AR positive), Caki-2 (AR positive), and the immortalized proximal tubule epithelial cell line from normal adult human kidney HK-2 and 293T (AR positive) were originally purchased from American Type Culture Collection (ATCC, Manassas, VA, USA) and preserved in our lab. All RCC cells were cultured in DMEM medium (Invitrogen, Carlsbad, CA, USA) supplemented with 10% fetal bovine serum (FBS) in the humidified 5% CO2 environment at 37 °C. SW839-VHL cell lines were stably transfected with VHL-wt cDNA into VHL-mut SW839 cells (ATCC). To generate LncRNA-SARCC overexpressing or LncRNA-SARCC knocked-down stable clones of SW839, SW839-VHL and OSRC-2 cells were transfected with lentiviral vectors, pWPI-LncRNA-SARCC vs. pWPI-Vec or pLKO1-sh-LncRNA-SARCC vs. pLKO1-shRNA-control, with the PAX2 packaging plasmid, and PMD2G envelope plasmid, then transfected into 293T cells for 48 hours to obtain the lentivirus soup followed by cryopreservation in −80 °C for later use. The cells were transfected using the lipofectamine 3000 (Invitrogen) reverse transfection protocol, according to the manufacturer’s instructions. Hypoxia—hypoxia (0.5% O2, 5% CO2, 94.5% N2) was achieved using an In Vivo2 hypoxic workstation (Ruskinn Technologies) or in a positive pressure chamber receiving gas from a custom-mixed tank (Airgas). Oxyrase® (Oxyrase) was used as a hypoxia mimetic at a final concentration of 100 mM while CoCl2 was used as a hypoxia mimetic at a final concentration of 200 µM. RNA immunoprecipitation (RIP)—native RIP was performed as described previously [50]. Briefly, SW839, SW839-VHL and OSRC-2 cells were lysed in RIPA lysis buffer (20 mM Tris-HCl/pH 7.5, 150 mM NaCl, 1 mM Na2EDTA, 1 mM EGTA, 1% NP-40, 1% sodium deoxycholate, 2.5 mM sodium pyrophosphate, 1 mM beta-glycerophosphate, 1 mM Na3VO4, 1 µg/mL leupeptin) supplemented with RNase inhibitor, protease inhibitor cocktail. RNase-free DNase (NEB) (400 U) was then added to the lysates and incubated on-ice for 30 minutes. The cell lysates were diluted in the RIPA buffer and 50 µL of the supernatant saved as input for PCR analysis. A total of 500 µL of the supernatant was incubated with 4 µg of AR antibody overnight (normal rabbit IgG as control). Protein A/G beads were pre-blocked by 15 mg/mL BSA in PBS. Then pre-blocked beads were added to the antibody-lysate mixture and incubated for another 2 hours. The RNA/antibody complex was washed four times by RIPA buffer supplemented with RNase inhibitor, protease inhibitor cocktail. The RNA was extracted using Trizol (Invitrogen) according to the manufacturer’s protocol and subjected to RT-qPCR analysis. For UV cross-linking and RIP, cells were first subjected to formaldehyde cross-linking and then native RIP protocol was conducted. RNA-pull down assay—LncRNA-SARCC, LncRNA-SARCC (1.6 kb), LncRNA-SARCC (1.2 kb) or LncRNA-SARCC (0.8 kb) were in vitro transcribed respectively from the PCR generated T7 promoter driven DNA fragments and biotin-labeled with the Biotin RNA Labeling Mix (Roche) and T7 RNA polymerase (Roche), treated with RNase-free DNase I (Roche), and purified with an RNeasy Mini Kit (Qiagen, Valencia, CA, USA). One milligram of whole-cell lysates from SW839 cells were incubated with 3 µg of purified biotinylated transcripts for 1 hour at 25 °C and complexes were isolated with streptavidin agarose beads (Invitrogen). The AR protein present in the pull-down material was detected by standard immunoblot analysis. Chromatin immunoprecipitation assay (ChIP)—cells were cross-linked with 4% formaldehyde for 10 minutes followed by cell collection and sonication with a predetermined power to yield genomic DNA fragments of 300–1,000 bp long. Lysates were precleared sequentially with normal rabbit IgG (sc-2027, Santa Cruz Biotechnology) and protein A-agarose. Anti-AR antibody (2.0 µg) was added to the cell lysates and incubated at 4 °C overnight. For the negative control, IgG was used in the reaction. Cell-cycle analysis—cells were plated at a density such that they would be 50% confluent on the day of analysis. Treatment (hypoxia) was then initiated over the next several days, so that all cells were in culture for the same amount of time and at similar confluency when harvested. BrdU analysis was performed following the standard protocol (Becton Dickinson) after a 20 min pulse with 10 mM BrdU. Cells were stained with Alexa 488 anti-BrdU (Invitrogen) and 0.1 M propidium iodide and analyzed in an LSR FACS machine (Becton Dickinson). For proliferation analysis with Hoechst staining, 104 cells were plated on 6-cm2 plates, with staining and counting done according to the manufacturer’s instructions (Invitrogen). Luciferase assay—cells were plated in 24-well plates and transfected with pGL3 reporter constructs using lipofectamine (Invitrogen) according to the manufacturer’s instruction. After transfection, DMEM media was added into the culture with dihydrotestosterone (DHT) with ethanol as vehicle control. pRL-TK was used as internal control. Luciferase activity was measured by Dual-Luciferase Assay (Promega) according to the manufacturer’s manual. Subcutaneous and renal capsule implantation—SW839 cells expressing pLKO1-sh-LncRNA-SARCC vs. pLKO1-shRNA-control (2×106) and SW839-VHL cells expressing pWPI-LncRNA-SARCC vs. pWPI-mock (2×106), were subcutaneously injected into one flank of 6-week-old male athymic nude mice (NCI) (n=8 mice per group). After 8–9 weeks, mice were sacrificed, and tumors were excised and weighed. Similarly, cells were injected into left renal capsule of 6-week-old male athymic nude mice (NCI) (n=8 mice per group). After 7–8 weeks, mice were sacrificed, and tumors were excised and weighed. Studies on animals were conducted with approval from the Animal Research Ethics Committee of the University of Rochester Medical Center. Statistical analysis—unless otherwise stated, all data were shown as mean ± SD. The SPSS 12.0 statistical software (SPSS Inc., Chicago, IL, USA) was applied for statistical analysis. The χ2 analysis and Fisher exact probability analysis were applied for comparison among the expression of AR, HIF-1α, HIF-2α, C-MYC and Ki-67 and individual clinicopathological features. Difference of tumor cells was determined by t test or analysis of variance.
(I) Hypoxia differentially regulates RCC cell proliferation in a VHL-dependent manner; (II) LncRNA-SARCC is differentially modulated by hypoxia in a VHL-dependent manner and is physically associated with AR; (III) LncRNA-SARCC interacts with AR and decreases AR protein stability; (IV) LncRNA-SARCC suppressed AR which alters HIF-2α/C-MYC signals under hypoxia; (V) mechanism dissection how AR modulates HIF-2α expression at the transcriptional level under hypoxia; (VI) mechanism dissection how HIF-2α modulates LncRNA-SARCC expression at the transcriptional level under hypoxia; (VII) LncRNA-SARCC differentially modulates RCC proliferation under hypoxia in the RCC in vivo mouse model.
LncRNA-SARCC is differentially regulated by hypoxia in a VHL-dependent manner both in tissue culture and in human RCC clinical samples. LncRNA-SARCC can suppress hypoxic cell cycle progression in the VHL-mutant RCC cells while derepress it in the VHL-restored RCC cells.
PMCID: PMC4842606
Renal cell carcinoma; LncRNA; hypoxia; androgen receptor
20.  Budd-Chiari syndrome in urology: Impact on nephrectomy for advanced renal cell carcinoma 
Budd-Chiari syndrome (BCS) is a poorly understood entity in urology. It results from obstruction of the hepatic veins and the subsequent complications. It has been infrequently reported to be secondary to hepatic venous obstruction from invasion by an inferior vena cava (IVC) tumor thrombus in renal cell carcinoma (RCC). We report the largest known series of patients with RCC and BCS.
Patients and Methods:
Ten patients presented to a tertiary hospital with locally advanced RCC with IVC tumor thrombus. All were evaluated and had clinical or radiographic evidence of BCS. All underwent nephrectomy, IVC thrombectomy or ligation, and tumor removal from the hepatic veins. The perioperative and pathological factors were measured. These included estimated blood loss (EBL) and transfusions. Inpatient factors including duration of intubation, length of intensive care unit (ICU) stay, and overall length of stay (LOS) were recorded. The tumor-free status was evaluated.
The average age was 59 years. No intraoperative deaths occurred. Two intraoperative complications were noted. The mean EBL was 4244 cc; mean surgery length was 8 hours 12 minutes; and the mean ICU stay was nine days. The overall LOS averaged 13.25 days. One patient died postoperatively of sepsis and multisystem organ failure. One patient required reoperation for an abdominal wall hematoma caused by subcutaneous enoxaparin administration. Average follow-up was 28 months. Five patients are alive with no evidence of disease.
Budd-Chiari syndrome is a rare entity in urology, with a potential for significant morbidity and mortality. Surgical excision of the primary tumor along with thrombectomy results in alleviation of BCS and improvement in the patient.
PMCID: PMC3193735  PMID: 22022058
Budd-Chiari syndrome; hepatic vein thrombus; inferior vena cava thrombus; renal cell carcinoma
21.  Squamous cell carcinoma in a duplicated renal pelvis 
We report an extremely rare case of squamous cell carcinoma (SCC) of the renal pelvis associated with an incompletely duplicated renal pelvis and ureter. A 71-year-old woman presented with left lower back pain and gross hematuria. Urinary cytology showed atypical squamous cells. Computed tomography, magnetic resonance imaging and retrograde pyelography revealed left incompletely duplicated renal pelvis and ureter and a mass in the left upper renal pelvis. A clinical diagnosis of left renal pelvic cancer was made and the patient underwent total nephroureterectomy. Histological examination of the resected specimen revealed SCC with marked keratinization in the upper renal pelvis. The tumor had invaded the renal parenchyma and perinephric fat. There was no urothelial carcinoma component. The pathological stage was pT4 N0. There was no evidence of recurrence 6 months postoperatively. Because the prognosis of SCC of the upper urinary tract is poor, urologists and pathologists should be aware that SCC may develop in duplicated urinary systems.
PMCID: PMC4270515  PMID: 25550838
Cancer; congenital anomaly; duplex kidney; immunohistochemistry; pathological diagnosis; prognosis
22.  Precise control of caval and hepatic vessels: Surgical technique to treat level III caval thrombus concomitant to renal cell carcinoma 
Canadian Urological Association Journal  2015;9(11-12):E808-E813.
We investigated the surgical techniques, safety, and prevention of complications of nephrectomy and removal of tumour thrombus for treating level III inferior vena cava (IVC) concomitant to renal cell carcinoma (RCC). We did this by precise controlling IVC and hepatic vessels without a vascular bypass.
In this series, we included 5 patients with level III IVC tumour thrombus below the hepatic vein concomitant to RCC. After precisely controlling the IVC and hepatic vessels, we then removed the thrombus en bloc with the renal vein. Blood loss volume, IVC clamping time, hypotension time, resuscitation, cardiocerebrovascular complications, and postoperative organ dysfunction were observed.
Surgery was successfully performed without perioperative death. Blood loss volume was 900 to 1500 mL, operation time was 165 to 250 minutes, vascular clamping time was 8 to 12 minutes, and intraoperative hypotension time was 9 to 12 minutes. Serious perioperative complications were not observed. Local recurrence was not observed during the 9 to 24 months of follow-up. One patient exhibited disease-free survival, 3 developed lung or liver metastasis, and 1 died 11 months after surgery.
Precise control of IVC and hepatic pedicle vessels, without vascular bypass, is a safe and effective surgical treatment for level III tumor thrombus below the hepatic vein concomitant to RCC. The procedure was conducted without increased risks of intraoperative hypotensive shock, difficult resuscitation, pulmonary embolism, and multiple organ dysfunctions.
PMCID: PMC4639433  PMID: 26600890
23.  Clinical versus Pathologic staging of Renal Tumors: Role of Multi-Detector CT Urography 
Electronic Physician  2016;8(1):1791-1795.
Our ability to diagnose renal cell carcinoma (RCC) has increased in the past 30 years as a result of the extensive application of imaging techniques, such as ultrasonography, computed tomography, and magnetic resonance imaging. Multi-detector computed tomography (MDCT) remains the most appropriate imaging modality for the diagnosis and staging of RCC. The aim of this work was to compare the findings of MDCT with surgical pathology to determine the accuracy of delineating tumor size, localization, organ confinement, lymph node metastases, and the extent of tumor thrombus in the renal vein and inferior vena cava.
The clinical, surgical, and anatomo-pathologic records of 99 patients treated by nephrectomy (radical or partial) for solid renal tumors at Theodor Bilharz Research Institute and Nasser Institute from 2005 to 2011 were reviewed retrospectively. All cases were staged pre-operatively with abdominal MDCT (pre- and post-contrast enhancement) in addition to the routine biochemical, hematological, and radiological work-up. The tumors’ histologic types were determined according to the WHO classification of renal tumors in adults in 2004, and staging was updated to the TNM 2010 system. Data were analyzed using the t-test.
The mean age was 52 (range 21–73). Seventy-eight patients were males, and 21 patients were females (Male/Female ratio: 3.7:1). There were no significant differences in the mean tumor size between radiographic and pathologic assessments in different tumor stages. The overall incidence of lymph node invasion in surgical specimens was 76%, whereas MDCT showed a positive incidence in 68.4% of cases (false negative result in 7 cases, 7.6%).
Our findings indicated that MDCT urography is an accurate method to estimate renal tumor size, lymph node, vascular and visceral metastases preoperatively. Also, preoperative staging of renal tumors with MDCT represents a valuable and accurate tool.
PMCID: PMC4768930  PMID: 26955451
Multi-Detector CT Urography; renal cell carcinoma; staging
24.  Renal Cell Carcinoma with Intraluminal Spread of the Entire Upper Urinary Tract 
Case Reports in Medicine  2013;2013:371387.
We describe an unusual case of renal cell carcinoma (RCC) involving the entire upper urinary tract. A 51-year-old female was referred to us because of macroscopic hematuria. Computed tomography revealed a renal tumor filling renal pelvis and ureter, which turned to be a clear cell RCC after nephroureterectomy.
PMCID: PMC3664473  PMID: 23737798
25.  MET Expression in Sporadic Renal Cell Carcinomas 
Journal of Korean Medical Science  2006;21(4):672-677.
Although germline mutations of met proto-oncogene on human chromosome 7q31-34 have been known as useful molecular markers of hereditary papillary renal cell carcinoma (RCC), the expression of MET, a product of met proto-oncogene, has not been fully studied in sporadic RCC, along with its clinical significance. We investigated the expression of MET by immunohistochemistry in 182 cases of renal neoplasm encompassing 145 RCC, 25 urothelial carcinomas of renal pelvis, and 12 oncocytomas. MET was diffusely and strongly expressed in 90% of papillary RCC, all collecting duct carcinomas, and 92% of urothelial carcinomas of renal pelvis. On the contrary, clear cell RCC, chromophobe RCC, and oncocytomas were negative or focally positive for MET expression. In clear cell RCC, MET expression was positively correlated with high nuclear grade, presence of infiltrative growth, tumoral necrosis, papillary architecture, sarcomatoid component, tumoral involvement of the renal pelvis or ureter, involvement of the calyx, and lymphatic invasion. In conclusion, diffuse and strong expression of MET in papillary RCC and collecting duct carcinoma might be helpful in discriminating from the other subtypes of RCC with tubular or papillary growth. In case of MET expression observed in clear cell RCC, it might correlate with those clinicopathological parameters implying aggressive behavior.
PMCID: PMC2729889  PMID: 16891811
Proto-Oncogene Proteins c-met; Carcinoma, Renal Cell; Kidney Neoplasms; Kidney; Immunohistochemistry

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