In Drosophila melanogaster, the fruitless (fru) gene encoding BTB-Zn-finger transcription factors organizes male sexual behavior by controlling the development of sexually dimorphic neuronal circuitry. However, the molecular mechanism by which fru controls the sexual fate of neurons has been unknown. Our recent study represents a first step toward clarification of this mechanism. We have shown that: (1) Fru forms a complex with the transcriptional cofactor Bonus (Bon), which recruits either of two chromatin regulators, Histone deacetylase 1 (HDAC1) or Heterochromatin protein 1a (HP1a), to Fru-target sites; (2) the Fru-Bon complex has a masculinizing effect on single sexually-dimorphic neurons when it recruits HDAC1, whereas it has a demasculinizing effect when it recruits HP1a; (3) HDAC1 or HP1a thus recruited to Fru-target sites determines the sexual fate of single neurons in an all-or-none manner, as manipulations of HDAC1 or HP1a expression levels affect the proportion of male-typical neurons and female-typical neurons without producing neurons of intersexual characteristics. Here, we hypothesize that chromatin landscape changes induced by ecdysone surges direct the HDAC1- or HP1a-containing Fru complex to distinct targets, thereby allowing them to switch the neuronal sexual fate in the brain.
courtship behavior; sexually dimorphic neurons; sexual fate; Fruitless; Bonus; HDAC1; HP1a
Anemia of inflammation (AI) is a common complication of rheumatoid arthritis (RA) and has a negative impact on RA symptoms and quality of life. Upregulation of hepcidin by inflammatory cytokines has been implicated in AI. In this study, we evaluated and compared the effects of IL-6 and TNF-α blocking therapies on anemia, disease activity, and iron-related parameters including serum hepcidin in RA patients.
Patients (n = 93) were treated with an anti-IL-6 receptor antibody (tocilizumab) or TNF-α inhibitors for 16 weeks. Major disease activity indicators and iron-related parameters including serum hepcidin-25 were monitored before and 2, 4, 8, and 16 weeks after the initiation of treatment. Effects of tocilizumab and infliximab (anti-TNF-α antibody) on cytokine-induced hepcidin expression in hepatoma cells were analyzed by quantitative real-time PCR.
Anemia at base line was present in 66% of patients. Baseline serum hepcidin-25 levels were correlated positively with serum ferritin, C-reactive protein (CRP), vascular endothelial growth factor (VEGF) levels and Disease Activity Score 28 (DAS28). Significant improvements in anemia and disease activity, and reductions in serum hepcidin-25 levels were observed within 2 weeks in both groups, and these effects were more pronounced in the tocilizumab group than in the TNF-α inhibitors group. Serum hepcidin-25 reduction by the TNF-α inhibitor therapy was accompanied by a decrease in serum IL-6, suggesting that the effect of TNF-α on the induction of hepcidin-25 was indirect. In in vitro experiments, stimulation with the cytokine combination of IL-6+TNF-α induced weaker hepcidin expression than did with IL-6 alone, and this induction was completely suppressed by tocilizumab but not by infliximab.
Hepcidin-mediated iron metabolism may contribute to the pathogenesis of RA-related anemia. In our cohort, tocilizumab was more effective than TNF-α inhibitors for improving anemia and normalizing iron metabolism in RA patients by inhibiting hepcidin production.
Methamphetamine is currently the most widespread illegal stimulant abused in the United States. No previous reports comparing echocardiographic findings of cardiomyopathy with and without a history of methamphetamine abuse are available.
We performed a single institution retrospective review of medical records and analyses of echocardiographic findings in patients ≤45 years of age hospitalized between 2001 and 2004 who were discharged with a diagnosis of cardiomyopathy or heart failure. After exclusion of patients with coronary artery disease or severe cardiac valvular disease, the remaining patients were divided into 2 groups based on their abuse or non abuse of methamphetamine, as determined by the documented history in the medical records or urine toxicology testing.
Among a total of 59 patients, 28 (47%) had a history of methamphetamine abuse or positive urine toxicology. Both methamphetamine abusers and non-abusers were predominately male (64.3% vs 64.5%, P = .99), and had a high prevalence of obesity (55.6% vs 73.3%, P = .16). Bivariate analysis revealed significant differences between the methamphetamine abusers and non-abusers in left atrium volume (119.7 ± 55.4 ml vs 85.8 ± 33.5 ml, P = .008), left ventricular end-diastolic volume (201.9 ± 71.4 ml vs 156.6 ± 63.1 ml, P = .01), left ventricular end-systolic volume (136.0 ± 53.7 ml vs 92.3 ± 55.8 ml, P = .004), right ventricular dimension (26.3 ± 6.0 mm vs 21.3 ± 6.0 mm, P = .007), and quantified left ventricular ejection fraction (32.9% ± 11.3% vs 44.6% ± 17.8%, P = .004).
We found a high prevalence of methamphetamine abuse in our study population. Methamphetamine abusers had echocardiographic findings of more severe dilated cardiomyopathy compared with non-abusers.
Nocturia is defined as waking one or more times during the night due to the urge to void. Recently, the effectiveness of several sedatives and analgesics for nocturia has been reported. We herein investigated the effects of ramelteon, an antioxidant and sleep inducer, on nocturia unresponsive to α1-blocker monotherapy in males with lower urinary tract symptoms (LUTS) as a pilot study.
Subjects were 19 patients who had LUTS suggestive of benign prostate hyperplasia, received α1-blockers (tamsulosin, silodosin, or naftopidil), and continued to have two or more episodes of nocturia per night before starting ramelteon. Ramelteon at 8 mg once daily for one month was added to the α1-blocker. A self-administered questionnaire including the International Prostate Symptom Score (IPSS), quality of life (QoL) index, Overactive Bladder Symptom Score (OABSS), and Nocturia Quality-of-Life Questionnaire (N-QOL) were assessed before and one month after starting ramelteon.
The mean score on IPSS question 7 (nocturia) decreased significantly from 2.88 before starting ramelteon to 2.41 one month after starting the medication (P = 0.03). The mean total OABSS decreased significantly from 6.31 to 5.38 (P = 0.03), and the mean for OABSS question 2 (nighttime frequency of nocturia) also significantly decreased from 2.63 to 2.13 (P = 0.01). The mean total N-QOL score did not change significantly. Two patients had dizziness; the remaining patients had no adverse drug-related events.
Ramelteon in combination with an α1-blocker could be a treatment option for reducing nocturia in men with BPH.
Ramelteon; Melatonin; Nocturia; Benign prostate hyperplasia; α1-blocker
To retrospectively assess the clinical utility in ureteroscopy (URS) planning of cumulative stone diameter (CSD), which does not account for stone width or depth, as a predictor of URS outcome and compare it with stone volume.
Materials and Methods
Patients with renal stones treated at a single institute by flexible URS were retrospectively evaluated. To assess the clinical utility of CSD, relationships between stone-free (SF) status and stone burden (CSD and volume) were analyzed using the area under the receiver operating characteristics (AUROC) curve. To identify stone number impact on CSD, the AUROC of CSD divided by stone number was evaluated. Correlation coefficients of CSD and stone volume were also calculated for groups by stone number.
In cases with CSD <20.0 mm, CSD and stone volume revealed equal ability to predict SF status. In cases with CSD ≥20.0 mm, stone volume showed higher predictive ability. The ROC curves for cases with ≥4 stones showed that CSD was less predictive of SF status than stone volume. The correlation coefficients of CSD and stone volume by stone number were 0.922 for 1 stone, 0.900 for 2–3 stones, and 0.661 for ≥4 stones.
In cases with CSD ≥20.0 mm or ≥4 stones, we should evaluate stone volume for a more predictive stone burden, and pretreatment non-contrast CT seems sufficient. In cases with CSD <20.0 mm or 1–3 stones, CSD was as valid a predictor of preoperative stone burden as stone volume, so preoperative kidney-ureter-bladder (KUB) films may be sufficient.
This study investigated the correlation between the operation time using two different power settings of a Ho: YAG laser.
A total of 68 patients underwent cystolithotripsy from April 2010 to October 2011 In Fifty-six of these patients underwent cystolithotripsy by one surgeon using a Ho: YAG laser for bladder calculi. This study assessed these patients in two groups; the 30 W laser generator group with the settings of 2.5 J x 5 Hz (30 W group) and the 100 W laser generator group as the settings of 3.5 J x 5 Hz (100 W group). The operation time in these two groups were assessed.
A total of 56 patients including 45 male and 11 female patients that underwent cystolithotripsy using a Ho: YAG laser for bladder calculi by one surgeon were enrolled in this study. The patients’ characteristics including age (mean; 68.8 vs 68.4 yr), gender (male; 74.2 vs 88.0%), stone burden (mean; 34.9 vs 41.3 mm), number of stones (mean; 3.2 vs 2.0) and stone’s CT density (mean; 981.5 vs 902.0 HU) showed no significant differences. All patients were stone free following treatment. The median total length of the operation was 19 minutes (mean: 34.6 ± 36.1) in the 30 W group and 29 minutes (mean: 44.4 ± 38.8) in the 100 W group, which was not significantly different.
The results showed that the power settings of Ho: YAG laser show no differences in the operation time for bladder calculi lithotripsy.
Cystolithotripsy; Ho; YAG laser; Bladder stone; Bladder calculi
To determine the impact of ureteroscopy-assisted retrograde nephrostomy (UARN) during percutaneous nephrolithotomy (PCNL).
Materials and Methods
From April 2009 to September 2011, a total of 50 patients underwent PCNL for large renal stones (stone burden >2 cm). We performed UARN in the Galdakao-modified Valdivia position for 27 patients (UARN PCNL) and ultrasonography-assisted percutaneous nephrostomy in the prone position for 23 patients (prone PCNL).
UARN PCNL significantly improved the stone-free rate (81.5% vs 52.2%) and the rate of residual stones (<4 mm, 92.6% vs 65.2%, P<0.05). The median length of the operation was significantly shorter for UARN PCNL, at 160 min, compared to 299 min for prone PCNL (P<0.001). There was one intraoperative complication in prone PCNL, namely a hemorrhage that resulted in stopping the initial treatment, but it was cured conservatively. The postoperative complications included a high grade fever that persisted for three days in two UARN PCNL patients (7.4%) and six prone PCNL patients (26.1%). The Clavien grading scores showed significantly lower postoperative complications for UARN PCNL compared to prone PCNL.
UARN is associated with a higher stone-free rate, shorter operation time, and fewer complications during PCNL than prone PCNL.
The authors studied the incremental value of adding serum cystatin C or creatinine to the Framingham risk score variables (FRSVs) for the prediction of incident cardiovascular disease (CVD) among 6,653 adults without clinical CVD utilizing the Multi-Ethnic Study of Atherosclerosis (2000–2008). CVD events included coronary heart disease, heart failure, stroke, and peripheral arterial disease. Variables were transformed to yield optimal prediction of 6-year CVD events in sex-stratified models with FRSVs alone, FRSVs + cystatin C, and FRSVs + creatinine. Risk prediction in the 3 models was assessed by using the C statistic, and net reclassification improvement was calculated. The mean ages were 61.9 and 64.6 years for individuals with and without diabetes, respectively. After 6 years of follow-up, 447 (7.2%) CVD events occurred. In the total cohort, no significant change in the C statistic was noted with FRSVs + cystatin C and FRSVs + creatinine compared with FRSVs alone, and net reclassification improvement for CVD risk was extremely small and not significant with the addition of cystatin C or creatinine to FRSVs. Similar findings were noted after stratifying by baseline presence of diabetes. In conclusion, the addition of cystatin C or serum creatinine to FRSVs does not improve CVD risk prediction among adults without clinical CVD.
cardiovascular diseases; creatinine; cystatin C; risk model
A 33-year-old male with an ileal conduit was referred to our department for the treatment of left renal calculi. After inserting a ureteral access sheath, a ureteroscopy-assisted retrograde nephrostomy was made. Percutaneous nephrolithotomy was successfully achieved using this nephrostomy.
Ureteroscopy; Ileal conduit; Lawson catheter; Retrograde nephrostomy; Urinary diversion
Introduction. Open surgical anatrophic nephrolithotomy (ANL) had been the standard treatment for large renal calculi prior to the development of endoscopic devices and endoscopic techniques. A previous report described the efficacy of ureteroscopy-assisted retrograde nephrostomy (UARN) and presented a case of renal calculi successfully treated with UARN during percutaneous nephrolithotomy (PCNL) in a patient after ANL. Case Presentation. A 61-year-old male with left renal calculi was referred for further treatment. The patient was placed under general and epidural anesthesia, in a Galdakao-modified Valdivia position. A flexible ureteroscope (URS) was inserted, and a Lawson retrograde nephrostomy puncture wire was advanced into the flexible URS. The puncture wire then followed the route from the renal pelvis to the exit skin. Calculus fragmentation was undertaken using a pneumatic lithotripter. Conclusions. UARN for PCNL was therefore found to be a safe, effective, and appropriate treatment for a patient presenting with renal calculi after undergoing ANL.
C-reactive protein (CRP) is considered a useful serum marker for patients with RCC. However, its clinical utility in advanced metastatic renal cell carcinoma (AM-RCC), particularly in deciding whether to perform nephrectomy at the onset, is not well studied.
Patients and methods
We retrospectively evaluated 181 patients with AM-RCC, including 18 patients underwent potentially curative surgery, 111 underwent cytoreductive nephrectomy, and 52 received medical treatment only. CRP cutoff points were determined by receiver operating characteristic (ROC) curve analysis. Kaplan-Meier and Cox regression analyses were used for survival tests.
ROC analysis suggested that grouping patients according to 3 CRP ranges was a rational model. Patients with highly elevated CRP (≥67.0 mg/L) presented remarkably poor prognosis despite treatment (nephrectomy or medical treatment only). Cox regression models demonstrated that risk factors of overall survival for patients who underwent nephrectomy were the CRP ranges defined in this study (≤18.0 mg/L, >18.0 and <67.0 mg/L, and ≥67.0 mg/L), ECOG PS (0, 1, and ≥2), and number of metastatic organ sites (0–1 and ≥2). The retrospective design is a limitation of this study.
Our study demonstrated that the serum CRP level is a statistically significant prognostic parameter for patients with AM-RCC. The data also indicated that pretreatment serum CRP level provides useful prognostic information that helps in deciding whether to perform initial nephrectomy for patients with AM-RCC.
C-reactive protein; Rena cell carcinoma; Prognosis
We previously reported on the effectiveness of ureteroscopy-assisted retrograde nephrostomy during percutaneous nephrolithotomy and report two cases of lower calyx calculi in horseshoe kidney that were successfully treated with ureteroscopy-assisted retrograde nephrostomy. During the ureteroscopy-assisted retrograde nephrostomy procedure, a ureteroscope is advanced in the desired calyx and a Lawson retrograde nephrostomy puncture wire is inserted. The wire is advanced through the calyx to exit the skin. The wire is then used for the percutaneous dilation.
Case 1 was a 68-year-old man who was shown on radiography to have left lower calyx calculi (19 × 15mm, 7 × 5mm, and 7 × 3mm) in horseshoe kidney. Case 2 was a 36-year-old woman shown on radiography to have a left lower calyx calculus (10 × 8mm) in horseshoe kidney.
Both patients were stone-free after ureteroscopy-assisted retrograde nephrostomy during percutaneous nephrolithotomy. Ureteroscopy-assisted retrograde nephrostomy is a promising procedure for safely and effectively treating lower calyx stones in horseshoe kidney.
Ureteroscopy; Horseshoe kidney; Lawson catheter; Retrograde nephrostomy; PCNL
A 23-year-old female had bilateral ureteral stents placed due to bilateral renal stones
and hydronephrosis. The bilateral ureteral stents were changed every 3 months. A
kidney ureter bladder (KUB) film showed left encrustation along the ureteral stent thus
necessitating removal; however, the ureteral stent could not be removed cystoscopically.
The ureteral stent was, therefore, extracted using flexible ureteroscopy (URS) with a
holmium (Ho): yttrium aluminum garnet (YAG) laser.
We developed a method for ureteral stent removal in female patients that requires no cystoscopy or fluoroscopic guidance using a crochet hook. In addition, we also investigated the success rate, complications and pain associated with this procedure.
A total of 40 female patients (56 stents) underwent the removal of ureteral stents. All procedures were carried out with the patients either under anesthesia, conscious sedation, or analgesic suppositories as deemed appropriate for each procedure including Shock Wave Lithotripsy (SWL), Ureteroscopy (URS), Percutaneous Nephrolithotomy (PCNL), and ureteral stent removal. At the time of these procedures, fluoroscopy and/or cystoscopy were prepared, but they were not used unless we failed to successfully remove the ureteral stent using the crochet hook. In addition, matched controls (comprising 50 stents) which were removed by standard ureteral stent removal using cystoscopy were used for comparison purposes.
A total of 47 of the 56 stents (83.9%) were successfully removed. In addition, 47 of 52 (90.4%) were successfully removed except for two migrated stents and two heavily encrusted stents which could not be removed using cystoscopy. Ureteral stent removal using the crochet hook technique was unsuccessful in nine patients, including two encrustations and two migrations. Concerning pain, ureteral stent removal using the crochet hook technique showed a lower visual analogue pain scale (VAPS) score than for the standard technique using cystoscopy.
Ureteral stent removal using a crochet hook is considered to be easy, safe, and cost effective. This technique is also easy to learn and is therefore considered to be suitable for use on an outpatient basis.
Patients with spinal cord injury and a chronic indwelling urinary catheter are known to have an increased risk of bladder malignancy. However, squamous cell carcinoma (SCC) of the epidermis around a suprapubic cystostomy is relatively rare. Here, we report a case of lower abdominal SCC arising from the suprapubic cystostomy tract.
A 58-year-old man with a complete spinal cord injury was referred to our hospital with a chief complaint of an abdominal mass. Abdominal enhanced computed tomography (CT) showed a 7-cm mass surrounding the suprapubic cystostomy and bilateral inguinal and para-aortic lymph nodes metastasis. Histopathological examination of percutaneous biopsy specimens was performed. The diagnosis was stage IV (cT4N1M1) epidermal SCC, which was treated with palliative external radiation therapy.
The SCC in this case was thought to arise from mechanical stimulus of the suprapubic cystostomy. Physicians and patients should pay careful attention to any signs of neoplasms with long-term indwelling catheters, such as skin changes around the suprapubic cystostomy site. This case presentation is only the fourth report of SCC arising from the suprapubic cystostomy tract in the literature. In cases of unresectable tumors and contraindications to chemotherapy, palliative radiotherapy may lead to disease remission and symptom relief.
Aim. Despite the beneficial effects of dietary restriction (DR) on lifespan, age-related diseases, including diabetes and cardiovascular diseases, its effects on type 2 diabetic nephropathy remain unknown. This study examined the renoprotective effects of DR in Wistar fatty (fa/fa) rats (WFRs).
Methods. WFRs were treated with DR (40% restriction) for 24 weeks. Urinary albumin excretion, creatinine clearance, renal histologies, acetylated-NF-κB (p65), Sirt1 protein expression, and p62/Sqstm 1 accumulation in the renal cortex, as well as electron microscopic observation of mitochondrial morphology and autophagosomes in proximal tubular cells were estimated.
Results. DR ameliorated renal abnormalities including inflammation in WFRs. The decrease in Sirt1 levels, increase in acetylated-NF-κB, and impaired autophagy in WFRs were improved by DR.
Conclusions. DR exerted anti-inflammatory effects and improved the dysregulation of autophagy through the restoration of Sirt1 in the kidneys of WFRs, which resulted in the amelioration of renal injuries in type 2 diabetes.
When retroperitoneoscopic radical nephrectomy for renal cell carcinoma was introduced into our institution, we performed a combined small skin incision method. In this method, a small incision was made to approach the retroperitoneal space prior to setting trockers and thereafter a LAPDISC was placed in the incision to start the retroperitoneoscopic procedure. In this study, we compared the outcomes between the combined small skin incision method ("A method" hereinafter) and the conventional method ("B method" hereinafter).
material and methods
Among the cases of T1N0M0 suspicious renal cell carcinoma treated at Yokohama City University between May 2003 and June 2009, the A method was performed in 51 cases and the B method was performed in 33 cases. The factors in the outcomes compared between the A and B methods were the duration of procedure, volume of bleeding, volume of transfusion, weight of the specimen, incidence of peritoneal injury, rate of conversion to open surgery, and perioperative complications.
The duration of the procedure was 214.4 ± 46.9 minutes in the A method group and 208.1 ± 36.4 minutes in the B method group (p = 0.518). The volume of bleeding and the weight of the specimen were 105.5 ± 283.2 ml and 335.1 ± 137.4 g in the A method group and 44.8 ± 116 ml (p = 0.247) and 309.2 ± 126 g (p = 0.385) in the B method group. There was no significant difference in all factors analyzed.
The A method would be highly possible to produce stable results, even during the introduction period when the staff and the institution are still unfamiliar with the retroperitoneoscopic surgery.
the retroperitoneoscopic radical nephrectomy method with a small incision; surgical outcome
Dialysis patients have a tendency to bleed, and clinicians sometimes encounter cases with a significant amount of spontaneous hemorrhage. We herein report two cases of spontaneous renal hemorrhage in hemodialysis patients.
A 70-year-old male who had received hemodialysis for 8 years presented with right abdominal pain. He had a history of renal failure due to diabetes mellitus. CT showed a right perirenal hemorrhage. Angiography revealed a right renal artery hemorrhage, and catheter embolization was performed.
A 76-year-old male who had undergone 7 years of continuous ambulatory peritoneal dialysis and 1 year of hemodialysis presented with right abdominal pain. He had a history of renal failure due to IgA nephropathy. CT showed a right perirenal hemorrhage. He received a blood transfusion and was put on absolute bed rest. At 2 days after admission, his anemia was found to have improved.
Renal hemorrhage; Hemodialysis; Spontaneous renal hematoma
In this study, by comparing TVT surgery and TOT surgery for stress urinary incontinence in women, the characteristics and learning curves of both operative methods were studied.
A total of 83 women with stress urinary incontinence treated with tension-free vaginal tape (TVT) (n = 38) or transobturator tape (TOT) (n = 45) at Saiseikai Central Hospital between April 2004 and September 2009 were included. We compare the outcomes and learning curves between TVT surgery and TOT surgery. In statistical analysis, Student's t test, Fisher's exact test, and Mann-Whitney's U test were used.
The surgical durations were 37.4 ± 15.7 minutes with TVT surgery and 31.0 ± 8.3 minutes with TOT surgery. A longer period of time was required for TVT surgery (p = 0.025). The residual urine at post-operative day 1 was higher in TVT surgery (25.9 ± 44.2 ml) than in TOT surgery (10.6 ± 19.2 ml) (p = 0.0452). The surgical duration of TVT surgery was shortened after the operator had performed 15 operations (p = 0.019).
In comparison of TVT surgery and TOT surgery, the surgical duration of TVT surgery was longer and the residual urine of TVT surgery was higher at post-operative day 1. Surgical experience could shorten the duration of TVT surgery.
Stress urinary incontinence; TVT surgery; TOT surgery
Catheter ablation is an evolving treatment option in patients with atrial fibrillation. Contrast enhanced electrocardiogram-gated multi-detector computed tomography (MDCT) has rapidly evolved over the past few years into an important tool in the diagnosis of coronary atherosclerosis. There is increasing recognition that MDCT is a useful tool to evaluate non-coronary structures, such as cardiac chambers, valves, the coronary sinus and adjacent structures including pulmonary veins. In particular, MDCT is playing an increasingly important role in the evaluation of the left atrium and the pulmonary veins in patients undergoing catheter ablation for atrial fibrillation. It provides accurate and reliable identification of the pulmonary veins and anatomical relationship between the left atrium and esophagus although the mobile esophagus may limit the value of MDCT to reduce the risk of atrio-esophagus fistula. In this article, we will review the evaluation of the left atrium and pulmonary veins using MDCT in patients undergoing catheter ablation of atrial fibrillation.
Cardiac imaging; Multi-detector computed tomography; left atrial volume; pulmonary veins; atrial fibrillation; catheter ablation.
Lobular carcinoma in situ (LCIS) clinically constitutes a risk factor for the subsequent development of either invasive lobular carcinoma (ILC) or invasive ductal carcinoma (IDC). In order to approach the possibility of this common precursor of both ILC and IDC, we investigated combined lobular and ductal carcinomas. Thirty-two cases of lobular carcinoma were picked up out of 773 cases of operated breast carcinomas. The histopathological detailed re-examination using immunostain of E-cadherin and β-catenin revealed a rather high frequency of combined lobular carcinomas than previous reports. Clinicopathologically, combined lobular carcinomas were younger and smaller than pure lobular carcinomas, and the cytological atypia was relatively low. These results suggested that combined lobular carcinomas could be detected in the earlier stage of breast cancer. Furthermore, the lobular and ductal components of combined carcinomas coexisted in the neighborhood and were distributed contiguously. The immunohistochemical phenotypes of both components were accorded in most combined cases. A genetic analysis using methylation-specific PCR on the HUMARA gene demonstrated that the same allele was inactivated in both lobular and ductal components in all detectable cases of combined carcinoma. Therefore, it is reasonable to assume that both lobular and ductal components of combined carcinomas are clonal and derived from the LCIS as the common precursor lesion, which may contradict the conventional concept that the lobular and ductal carcinomas arise from distinct differentiation pathways.
breast cancer; ductal carcinoma; human androgen receptor (HUMARA) gene; lobular carcinoma; methylation-specific PCR