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1.  Melanotic Oncocytic Metaplasia of the Nasopharynx: A Report of Three Cases and Review of the Literature 
Korean Journal of Pathology  2012;46(2):201-204.
Melanotic oncocytic metaplasia of the nasopharynx is a rare condition which is characterized by the presence of usually a small, brown to black colored pigmented lesion around the Eustachian tube opening. Although it is a benign lesion, it may be clinically misdiagnosed as malignant melanoma. Microscopically, melanotic oncocytic metaplasia is a combination of oncocytic metaplasia of the epithelium of the gland and melanin pigmentation in its cytoplasm. In our present study, we report three cases of melanotic oncocytic metaplasia of the nasopharynx. All the three cases occurred in men and were presented as multiple black pigmented lesions around the torus tubarius. Microscopically, mucous glands with diffuse oncocytic metaplasia and numerous black pigments were observed. No cellular atypia was observed. Immunohistochemically, the scattering of S-100 protein-positive, and human melanoma black 45-negative dendritic melanocytes was evident. This is the first report of cases of melanotic oncocytic metaplasia of the nasopharynx in Korea.
doi:10.4132/KoreanJPathol.2012.46.2.201
PMCID: PMC3479774  PMID: 23110002
Metaplasia; Oxyphil cells; Melanins; Nasopharynx
2.  Cytoplasmic mislocalization of overexpressed FOXF1 is associated with the malignancy and metastasis of colorectal adenocarcinomas 
Our previous studies have revealed that the human FOXF1 gene, encoding a transcription factor member of the forkhead box (FOX) family, functions as a tumor suppressor and its expression is frequently silenced in breast cancer via DNA hypermethylation. Moreover, we recently reported that FOXF1 expression is preferentially silenced in colorectal cancer cell lines with inactive p53 and knockdown of FOXF1 caused genomic instability in FOXF1-expressing colorectal cancer cells with a defect in the p53-p21WAF1 checkpoint, suggesting that FOXF1 plays a key role in colorectal tumorigenesis. Given that the in vivo role of FOXF1 in colorectal cancer remains unknown, the study here was aimed at delineating the clinical relevance of FOXF1 in colorectal adenocarcinomas. To characterize FOXF1 protein expression in colorectal cancer, designed tissue microarrays, comprising 50 cases of primary colorectal adenocarcinoma paired with matched adjacent normal tissue, were utilized in the immunohistochemistry (IHC) study. The IHC results showed that for adjacent normal colorectal tissue, the FOXF1 protein was only detected in stroma, not in epithelium, with either cytoplasmic staining (70% of total cases) or a mix of cytoplasmic and nuclear staining (6%). In contrast, for colorectal adenocarcinomas, FOXF1 staining was predominately identified in the cytoplasm of tumor epithelial cells (40% of total cases) and tumor-associated stromal cells of some cases (10%) also exhibited FOXF1 positivity in their cytoplasm. Cytoplasmic FOXF1 protein expression in tumor epithelial cells positively correlated with the histologic grade, depth of invasion, stage and lymphatic metastasis of colorectal adenocarcinomas (p < 0.05). Moreover, in silico meta-analysis of Oncomine’s cancer microarray database indicates that FOXF1 mRNA is overexpressed in a significant subset of colorectal adenocarcinoma tumors compared with normal colorectal tissue and other types of cancers. Our findings for the first time have revealed that the FOXF1 protein is overexpressed as well as mislocalized in cancerous epithelial cells and underexpressed/lost in tumor-associated stromal fibroblasts of colorectal adenocarcinomas, and suggest that FOXF1 is a potential prognostic marker due to its association with the malignancy and metastasis of colorectal cancer.
doi:10.1016/j.yexmp.2012.10.014
PMCID: PMC3562381  PMID: 23103611
colorectal cancer; FOXF1; tumor suppressor gene; tissue microarrays; immunohistochemistry; cytoplasmic mislocalization
3.  Invasive Cystic Hypersecretory Carcinoma of the Breast: A Case Report 
Journal of Korean Medical Science  2004;19(1):149-151.
Cystic hypersecretory lesions of the breast are rare. These breast lesions include cystic hypersecretory hyperplasia (CHH), atypical CHH, and cystic hypersecretory carcinoma (CHC). The characteristic features are dilated ducts and cysts filled with thyroid colloid-like eosinophilic secretion. Only seven cases of invasive CHC have been reported in the literature. Here, we report an additional case of invasive CHC. The histologic features of the tumor showed both micropapillary intraductal carcinoma and focal high-grade invasive carcinoma in a background of CHH. This case suggests that cystic hypersecretory breast lesions encompass a spectrum of pathologic lesions including CHH, atypical CHH, CHC, and invasive CHC.
doi:10.3346/jkms.2004.19.1.149
PMCID: PMC2822254  PMID: 14966360
Breast; Neoplasms; Carcinoma; Cystic Hypersecretory Carcinoma; Cystic Hypersecretory Hyperplasia
4.  Malignant thyroid bed mass after total thyroidectomy 
Purpose
Ultrasonographic (US) criteria on malignant thyroid bed mass have been suggested, including taller than wide shape, loss of echogenic hilum, abnormal vascularity, and microcalcification. The relationship between fine-needle aspiration (FNA) cytology findings and US findings on thyroid bed mass is unknown. We have retrospectively assessed the malignant thyroid bed mass after total thyroidectomy due to papillary thyroid carcinoma (PTC).
Methods
We retrospectively evaluated 2,048 patients who underwent total thyroidectomy due to PTC. FNA was performed in 97 patients on the thyroid bed under US surveillance. The 97 suspicious thyroid bed masses were divided into two groups: metastatic thyroid bed group (n = 34) and nonmetastatic group (n = 63). The groups were evaluated according to various clinical, serologic, and US findings.
Results
Within a median 47.0 months of follow-up, the proportion of malignant thyroid bed mass was high in large tumor size (1.37 cm vs. 1.03 cm), isthmic position (10.3% vs. 3.9%), and previous N1a (55.9% vs. 34.9%). US findings revealed that the presence of microcalcification or macrocalcification (47.1% vs. 19.0%) and thyroid bed mass height (5.4 mm vs. 3.9 mm) were the only discriminable criteria for central compartment recurrence. But, degree of echogenicity, loss of hilum, and irregularity of margin failed to discriminate malignant thyroid bed mass.
Conclusion
US findings on malignant thyroid bed mass were different from previously reported general criteria on lateral metastatic nodes. Additional FNA cytology should be performed on patients, even low-risk patients, who present the above findings.
doi:10.4174/jkss.2013.85.3.97
PMCID: PMC3764368  PMID: 24020017
Ultrasonography; Fine-needle biopsy; Thyroidectomy; Papillary thyroid cancer
5.  Hoxb7 Inhibits Transgenic HER-2/neu–Induced Mouse Mammary Tumor Onset but Promotes Progression and Lung Metastasis 
Cancer research  2008;68(10):3637-3644.
Our previous studies have shown that HOXB7 mRNA is overexpressed in ~50% of invasive breast carcinomas and promotes tumor progression in breast cancer cells grown as xenografts in mice. In silico analysis of published microarray data showed that high levels of HOXB7 predict a poor outcome in HER-2–positive (P = 0.046), but not in HER-2–negative breast cancers (P = 0.94). To study the function of HOXB7 in vivo in the context of HER-2 overexpression, we generated mouse mammary tumor virus (MMTV)-Hoxb7 transgenic mice, and then crossed them with MMTV-HER-2/neu transgenic mice. In the mice carrying both Hoxb7 and HER-2/neu transgenes, Hoxb7 plays a dual role in mammary tumorigenesis. In double transgenic mice, overexpression of Hoxb7 delayed tumor onset and lowered tumor multiplicity. However, consistent with the clinical data, once the tumors appeared, their growth was faster and metastasis to the lungs occurred at a higher frequency. Our data show, for the first time, that deregulated expression of Hoxb7 in mammary tumor cells can significantly modulate HER-2/neu-oncogene induced tumorigenesis in vivo.
doi:10.1158/0008-5472.CAN-07-2926
PMCID: PMC3715065  PMID: 18463397
6.  Invasive Micropapillary Carcinoma of the Breast: MR Imaging Findings 
Korean Journal of Radiology  2013;14(4):551-558.
Objective
To analyze the magnetic resonance (MR) imaging findings of invasive micropapillary carcinoma of the breast.
Materials and Methods
MR images were retrospectively evaluated in 14 patients (age range: 37-67, mean age: 49 years) with pathologically confirmed invasive micropapillary carcinoma of the breast. The enhancement type (mass/non-mass), shape, margin, contrast enhancement, and time-intensity curve pattern on the dynamic study were correlated with the histopathologic features. Associated findings, such as edema, nipple change, skin change and enlarged axillary lymph nodes were also studied.
Results
The most common features of the masses were irregular shape (12 of 14 patients, 85.8%) and irregular or spiculated margin (11 of 14 patients, 78.7%). The contrast enhancement was heterogeneous in 11 patients (78.7%), rim enhancement in 2 cases (14.2%), and homogeneous in one patient (7.1%). The predominant kinetic pattern was rapid increase (14 of 14, 100%) in the initial phase and washout (11 of 14, 78.7%) in the delayed phase. Associated non-mass like enhancement was shown in 4 patients, representing ductal carcinoma in situ. MR imaging helped detect additional sites of cancer other than the index lesion in 3 patients (21.4%). Enlarged axillary lymphadenopathy was identified in 7 of the 14 patients (50%).
Conclusion
Invasive micropapillary carcinoma appears as a mass with an irregular shape, irregular or spiculated margin and heterogeneous enhancement on MR imaging. Though these findings are not specific and are also observed with other breast malignancies, invasive micropapillary carcinoma frequently showed multiple lesions, accompanying non-mass enhancement and axillary lymph node enlargement.
doi:10.3348/kjr.2013.14.4.551
PMCID: PMC3725348  PMID: 23901311
Breast neoplasms; Diagnosis; Micropapillary carcinoma; Breast neoplasms; MR
7.  Subcutaneous Panniculitis-Like T-Cell Lymphoma of the Breast 
Korean Journal of Radiology  2013;14(3):391-394.
Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of cutaneous lymphoma. There have been a few case reports describing the radiologic imaging findings of SPTCL. We report a case of SPTCL, rarely presented with a breast mass. Here, we review her clinical history and radiologic (mammography and ultrasound) findings.
doi:10.3348/kjr.2013.14.3.391
PMCID: PMC3655289  PMID: 23690702
Subcutaneous panniculitis-like T-cell lymphoma; Breast; Mammography; Ultrasound
8.  The p53-p21WAF1 checkpoint pathway plays a protective role in preventing DNA rereplication induced by abrogation of FOXF1 function 
Cellular signalling  2011;24(1):316-324.
We previously identified FOXF1 as a potential tumor suppressor gene with an essential role in preventing DNA rereplication to maintain genomic stability, which is frequently inactivated in breast cancer through the epigenetic mechanism. Here we further addressed the role of the p53-p21WAF1 checkpoint pathway in DNA rereplication induced by silencing of FOXF1. Knockdown of FOXF1 by small interference RNA (siRNA) rendered colorectal p53-null and p21WAF1-null HCT116 cancer cells more susceptible to rereplication and apoptosis than the wild-type parental cells. In parental HCT116 cells with a functional p53 checkpoint, the p53-p21WAF1 checkpoint pathway was activated upon FOXF1 knockdown, which was concurrent with suppression of the CDK2-Rb cascade and induction of G1 arrest. In contrast, these events were not observed in FOXF1-depleted HCT116-p53−/− and HCT116-p21−/− cells, indicating the p53-dependent checkpoint function is vital for inhibiting CDK2 to induce G1 arrest and protect cells from rereplication. The pharmacologic inhibitor (caffeine) of Ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3 related (ATR) protein kinases abolished activation of the p53-p21WAF1 pathway upon FOXF1 knockdown, suggesting that suppression of FOXF1 function triggered the ATM/ATR-mediated DNA damage response. Cosilencing of p53 by siRNA synergistically enhanced the effect of FOXF1 depletion on stimulation of DNA rereplication and apoptosis in wild-type HCT116. Finally, we show that FOXF1 expression is predominantly silenced in breast and colorectal cancer cell lines with inactive p53. Our study demonstrated that the p53-p21WAF1 checkpoint pathway is an intrinsically protective mechanism to prevent DNA rereplication induced by silencing of FOXF1.
doi:10.1016/j.cellsig.2011.09.017
PMCID: PMC3205208  PMID: 21964066
FOXF1; tumor suppressor gene; DNA rereplication; p53; p21WAF1
9.  HER2 Status by Standardized Immunohistochemistry and Silver-Enhanced In Situ Hybridization in Korean Breast Cancer 
Journal of Breast Cancer  2012;15(4):381-387.
Purpose
Amplification of the human epidermal growth factor receptor 2 (HER2) gene occurs in 18% to 20% of breast cancers, and it is recognized as a prognostic and predictive marker. We investigated the HER2 status in Korean breast cancer by immunohistochemistry (IHC) and silver-enhanced in situ hybridization (SISH), as the first step toward building a nationwide quality assurance program for HER2 testing.
Methods
A total of 1,198 breast carcinoma samples were collected from six institutions and IHC and SISH were performed using tissue microarrays in central laboratories. The results were compared to those of local laboratories.
Results
Available data were obtained from 959 samples. Central IHC results were negative, equivocal, and positive for 756 (78.8%; range among institutions, 76.8-81.8%), 37 (3.9%; 1.9-6.2%), and 166 (17.3%; 13.6-20%), respectively. SISH results were negative, equivocal, and positive for 756 (78.8%; 77.4-79.9%), 2 (0.2%; 0-0.7%), and 201 (21%; 20.1-22.2%), respectively. HER2 gene amplification was observed in 4.4%, 19%, and 73.9% of the negative, equivocal and positive groups stratified by local IHC results, respectively. When central SISH was considered to be the gold standard method for measuring HER2 status, the false-negative and false-positive rates of local IHC were 14.4% (29/201) and 7.1% (54/756). The concordance rate between central IHC and SISH was 98.4%.
Conclusion
Central IHC and SISH markedly decreased the interlaboratory variability of HER2 status and the results of the two were highly concordant. The quality control program for HER2 testing must be focused on decreasing both the false negativity and positivity of IHC in local laboratories.
doi:10.4048/jbc.2012.15.4.381
PMCID: PMC3542844  PMID: 23346165
Breast neoplasms; HER2 gene; Immunohistochemistry; Silver-enhanced in situ hybridization
10.  Age and prognosis of papillary thyroid carcinoma: retrospective stratification into three groups 
Purpose
We investigated the prognosis according to age in papillary thyroid carcinoma (PTC) patients.
Methods
We retrospectively evaluated 2,890 patients who underwent thyroidectomy due to PTC between May 2004 and Aug 2008. We divided patients into 3 groups: young (≤35 years old), middle (between 35 and 54 years old), and old (≥55 years old).
Results
Median age was 47.0 years old (range, 15 to 82 years). Within a follow-up period median of 50 months, there were 148 (5.1%) locoregional recurrences, 6 (0.2%) PTC-related deaths, and 18 (0.6%) PTC-unrelated deaths. Outcomes were more favorable in the young group, with no PTC-related death despite the frequent locoregional recurrence. In the old group compared to the middle, there was a higher proportion of male, and more aggressive types as T3 or N1b, higher mean tumor number, more multiplicity, and bilaterality. The old group of ≥55 years did not show a significant difference in PTC-related deaths than other age groups in Cox analysis (OR, 0.9; P = 0.677), but a significant cutoff age in PTC-related deaths at 62.5 years was determined in ROC analysis (area under curve = 0.912).
Conclusion
We showed that the ≤35 years group shows favorable prognosis despite the frequent locoregional recurrence and ≥62.5 years group shows a poor prognosis regardless of other factors such as male sex or tumor aggressiveness. Further multiinstitutional studies are needed to elucidate the prognosis according to patient's age.
doi:10.4174/jkss.2012.83.5.259
PMCID: PMC3491227  PMID: 23166884
Age; Prognosis; Papillary thyroid carcinoma
11.  Observational study of central metastases following thyroid lobectomy without a completion thyroidectomy for papillary carcinoma 
Purpose
There are no guidelines for the optimal timing of the decision of when to perform completion thyroidectomy, and controversy exists regarding how the timing of completion thyroidectomy impacts survival patterns. We investigated the legitimacy of an observational strategy in central node metastasis after thyroid lobectomy for papillary thyroid cancer (PTC).
Methods
We retrospectively evaluated 522 consecutive patients who underwent thyroid lobectomy. Of the 69 patients with central metastasis, 61 patients (88.4%) were included in an observational study under cautious evaluation with informed consent by the patients, and compared with an observation arm of 180 postlobectomy N0 (node negative proven) patients.
Results
Of the 522 patients, six (1.1%) thyroid, five (0.9%) central, and two (0.4%) lateral recurrences were observed. Lateral recurrences occurred in the immediate completion N0 and Nx groups but not in the N1a observation arms. There were two (3.3%) central recurrences without thyroid or lateral recurrence on the observation arm of N1a observation patients. But two (1.1%) thyroid and three (1.7%) central recurrences were on the observation arm of N0 patients. In Kaplan-Meier survival curves for central or lateral recurrences between observation arms for the N1a and N0 groups, no significant difference was found between the N1a and N0 observation arms (P = 0.365).
Conclusion
The timing of when to perform completion thyroidectomy in central metastases-proven patients after lobectomy for PTC should be based on the patient's risk category.
doi:10.4174/jkss.2012.83.4.196
PMCID: PMC3467385  PMID: 23091791
Observation; Lymphatic metastasis; Thyroid neoplasms; Thyroidectomy
12.  Primary papillary carcinoma originated from a branchial cleft cyst 
Journal of the Korean Surgical Society  2011;81(Suppl 1):S12-S16.
Although branchial cleft cysts are common, papillary carcinomas arising from them are rare. Here we report a 41-year-old woman with papillary carcinoma originating from a right lateral branchial cleft cyst without any evidence of a papillary carcinoma in the thyroid gland. The patient underwent right lateral neck dissection followed by total thyroidectomy. We then confirmed papillary carcinoma arising from the branchial cleft cyst through microscopic and immunohistochemical staining with thyroglobulin (TG), thyroid-associated transcription factor-1 (TTF-1) and p63. It is the 10th case worldwide describing papillary carcinoma in a branchial cleft cyst with a review of the literature on the features of the disease and discussion of the role of immunohistochemical staining with TG, TTF -1 and p63. In conclusion, it should be emphasized that the surgeon must be cautioned of the possibility of primary papillary carcinoma in the branchial cleft cyst.
doi:10.4174/jkss.2011.81.Suppl1.S12
PMCID: PMC3267057  PMID: 22319730
Branchioma; Thyroid neoplasms; Papillary carcinoma
13.  Thyroid gland metastasis arising from primary liver cholangiocarcinoma: The first case report involving surgical operation 
Introduction
A primary cancer causing thyroid metastasis is extremely rare. In western countries, the most common primary tumors causing thyroid metastases include kidney, lung, breast, and gastrointestinal cancers. In contrast, breast is the most common primary site, followed by kidney, colon, and lung cancers in Korea. To the best of our knowledge, surgically confirmed thyroid metastasis from cholangiocarcinoma has not been reported. Herein, we report the first case of thyroid metastasis secondary to cholangiocarcinoma on which surgery was performed.
Presentation of case
A 55-year-old man was diagnosed with hepatic malignancy in December 2008. He subsequently received 2 cycles of transarterial chemoembolization and 4 cycles of radio-frequency ablation between 2008 and 2010. At follow-up in January 2011, brain metastasis was identified in the right parietal area secondary to cholangiocarcinoma. In April 2011, the patient was found to have palpable masses on the left thyroid and lateral neck. The patient subsequently underwent total thyroidectomy followed by left radical neck dissection. Intraoperatively, an ill-defined mass measuring 6.0 cm was found infiltrating the subcutaneous tissue into the prevertebral fascia. Microscopic and immunohistochemical findings confirmed that the thyroid masses and lymph nodes were metastatic cholangiocarcinoma.
Discussion
Positive immunohistochemical staining for cytokeratin 7, cytokeratin 19, and AFP and negative results for TG, TTF-1, and cytokeratin 20 can be definitely helpful in arriving at a correct diagnosis.
Conclusion
To the best of our knowledge, this is the first case report on surgically resected thyroid and lateral neck metastases secondary to cholangiocarcinoma.
doi:10.1016/j.ijscr.2011.11.001
PMCID: PMC3267264  PMID: 22288052
Neoplasm metastasis; Thyroid metastasis; Cholangiocarcinoma
14.  A Case of Metastatic Renal Cell Carcinoma to Thyroid Gland 
Chonnam Medical Journal  2011;47(2):130-133.
Metastasis to the thyroid gland from distant cancer is rare, and, in some cases, is a diagnostic challenge. Here, we report a case of metastatic renal cell carcinoma of the thyroid gland. A 77-year-old man presented with a neck mass detected about 1 month previously. He had undergone a right nephrectomy owing to renal cell carcinoma 14 years previously. Fine needle aspiration cytology showed a few atypical follicular cells with nuclear atypia. Under a tentative diagnosis of papillary thyroid carcinoma, a total thyroidectomy was performed. The histologic and immunohistochemical studies of the surgical specimens indicated that the thyroid masses were metastatic renal cell carcinoma to the thyroid.
doi:10.4068/cmj.2011.47.2.130
PMCID: PMC3214867  PMID: 22111075
Metastasis; Renal cell carcinoma; Thyroid cancer
15.  Epigenetic inactivation of the potential tumor suppressor gene FOXF1 in breast cancer 
Cancer research  2010;70(14):6047-6058.
The expression of several members of the FOX gene family is known to be altered in a variety of cancers. We show that in breast cancer, FOXF1 gene is a target of epigenetic inactivation and that its gene product exhibits tumor suppressive properties. Loss or downregulation of FOXF1 expression is associated with FOXF1 promoter hypermethylation in breast cancer cell lines and in invasive ductal carcinomas (IDCs). Methylation of FOXF1 in IDC (37.6% of 117 cases) correlated with high tumor grade. Pharmacologic unmasking of epigenetic silencing in breast cancer cells restored FOXF1 expression. Re-expression of FOXF1 in breast cancer cells with epigenetically silenced FOXF1 gene led to G1 arrest concurrent with or without apoptosis to suppress both in vitro cell growth and in vivo tumor formation. FOXF1-induced G1 arrest resulted from a blockage at G1-S transition of cell cycle through inhibition of the CDK2-RB-E2F cascade. Si-RNA-mediated depletion of FOXF1 in breast cancer cells led to increased DNA rereplication, suggesting that FOXF1 is required for maintaining the stringency of DNA replication and genomic stability. Further, expression profiling of cell-cycle regulatory genes showed that abrogation of FOXF1 function resulted in increased expression of E2F-induced genes involved in promoting progression of S and G2 phases. Therefore, our studies have identified FOXF1 as a potential tumor suppressor gene that is epigenetically silenced in breast cancer, which plays an essential role in regulating cell cycle progression to maintain genomic stability.
doi:10.1158/0008-5472.CAN-10-1576
PMCID: PMC2909657  PMID: 20587515
FOXF1; breast cancer; epigenetic silencing
16.  Basal-like breast cancer displays distinct patterns of promoter methylation 
Cancer biology & therapy  2010;9(12):1017-1024.
Recent microarray profiling studies on breast cancer have identified distinct subtypes that are associated with different clinical outcomes. Promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during the pathogenesis of breast cancer. We proposed that immunohistopathologic subtypes of breast cancer are likely to contain distinct promoter methylation patterns. A panel of ten gene promoters was assessed by quantitative multiplex methylation-specific PCR in 114 invasive ductal carcinomas from Korea representing the three major subtypes [57 luminal, 24 human epidermal growth factor 2 (HER2), and 33 basal-like] based on immunohistochemical findings of estrogen receptor, progesterone receptor, HER2, cytokeratin 5/6 and epidermal growth factor receptor. The median methylation levels of HIN1, RASSF1A and TWIST, and the average methylation ratio were significantly lower in basal-like subtype compared to luminal or HER2 subtypes. In contrast, BRCA1 methylation level was significantly higher in basal-like subtype than in luminal subtype. The methylation status of a panel of four genes (APC1, CDH, BRCA1 and RAR-β) in luminal and HER2 subtypes were dissimilar, where HER2 tumors showed a significantly higher level of methylation compared to luminal tumors. These results suggest that gene methylation in breast cancer can potentially serve as epigenetic biomarkers and may contribute further to current breast cancer classification.
PMCID: PMC3094906  PMID: 20505321
breast cancer; basal-like; luminal; HER2; methylation; quantitation
17.  A sclerosing stromal tumor of the ovary with masculinization in a premenarchal girl 
Korean Journal of Pediatrics  2011;54(5):224-227.
A sclerosing stromal tumor of the ovary is an extremely rare benign tumor; it usually is found during the second and third decades of life. Patients present with pelvic pain or a palpable abdominal mass. Hormonal effects such as masculinization are uncommon. Here, an 11-year old premenarchal girl presented with deepening of the voice. In addition, clitoromegaly and hirsutism with a male suprapubic hair pattern were observed. The laboratory findings showed that the testosterone level was elevated to 3.67 ng/mL, andostenedione to above 10 ng/mL, dehydroepiandrosterone-sulfate to 346 µg/dL and 17-hydroxy progesterone (17-OHP) to 11.28 ng/mL. The chromosome evaluation revealed a 46,XX female karyotype. An adrenocorticotropic hormone stimulation test was performed. The 17-OHP to cortisol ratio in 30 minutes was 0.045, which suggested a heterozygote for the 21-hydroxylase deficiency. However, the CYP21A2 gene encoding steroid 21-hydroxylase showed normal. The pelvic ultrasound showed a heterogeneous mass consisting of predominantly solid tissue in the pelvic cavity. The pelvic magnetic resonance imaging revealed an 8.9×6.2×6.6 cm mass of the left ovary. A left oophrectomy was performed and microscopic examination confirmed a sclerosing stromal tumor. Immunohistochemical studies showed that the tumor was positive for smooth muscle actin and vimentin, but negative for S-100 protein and cytokeratin. Following surgery, the hormone levels returned to the normal range and the hirsutism resolved.
doi:10.3345/kjp.2011.54.5.224
PMCID: PMC3145908  PMID: 21829415
Ovary; Ovarian neoplasms; Sex cord-gonadal stromal tumors; Virilism
18.  SLITs Suppress Tumor Growth In vivo by Silencing Sdf1/Cxcr4 within Breast Epithelium 
Cancer research  2008;68(19):7819-7827.
The genes encoding Slits and their Robo receptors are silenced in many types of cancer, including breast, suggesting a role for this signaling pathway in suppressing tumorigenesis. The molecular mechanism underlying these tumor-suppressive effects has not been delineated. Here, we show that loss of Slits, or their Robo1 receptor, in murine mammary gland or human breast carcinoma cells results in coordinate up-regulation of the Sdf1 and Cxcr4 signaling axis, specifically within mammary epithelium. This is accompanied by hyperplastic changes in cells and desmoplastic alterations in the surrounding stroma. A similar inverse correlation between Slit and Cxcr4 expression is identified in human breast tumor tissues. Furthermore, we show in a xenograft model that Slit overexpression down-regulates CXCR4 and dominantly suppresses tumor growth. These studies classify Slits as negative regulators of Sdf1 and Cxcr4 and identify a molecular signature in hyperplastic breast lesions that signifies inappropriate up-regulation of key prometastatic genes.
doi:10.1158/0008-5472.CAN-08-1357
PMCID: PMC3075571  PMID: 18829537
19.  VEGF as a Predictor for Response to Definitive Chemoradiotherapy and COX-2 as a Prognosticator for Survival in Esophageal Squamous Cell Carcinoma 
Journal of Korean Medical Science  2011;26(4):513-520.
We investigated the patterns of pretreatment expression of the epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2) by immunohistochemical staining and determined their correlation with treatment response and survival in 44 patients with esophageal squamous cell carcinoma (ESCC) treated with definitive concurrent chemoradiotherapy (CCRT). The definitive CCRT consisted of a median dose of 54 Gy (range: 40.0-68.4 Gy) and two cycles of concurrent administration of mostly 5-fluorouracil + cisplatinum. High expression of EGFR, VEGF, and COX-2 was found in 79.5%, 31.8%, and 38.6%, respectively. The Cox regression analysis for overall survival (OS) showed that both the treatment response and COX-2 expression were significant. The 3-yr OS rates of patients that achieved a complete response and those that did not were 46.7% and 5.3%, respectively (P = 0.006). The logistic regression analysis for treatment response with various parameters showed that only a high expression of VEGF was significantly associated with a complete response. Unlike other well-known studies, higher expression of VEGF was significantly correlated with a complete response to CCRT in this study. However, higher expression of COX-2 was significantly associated with shorter survival. These results suggest that VEGF might be a predictive factor for treatment response and COX-2 a prognostic factor for OS in patients with ESCC after definitive CCRT.
doi:10.3346/jkms.2011.26.4.513
PMCID: PMC3069570  PMID: 21468258
Esophageal Neoplasms; Chemoradiotherapy; Epidermal Growth Factor Receptor; Vascular Endothelial Growth Factor; Cyclooxygenase 2
20.  Papillary Thyroglossal Duct Cyst Carcinoma with Synchronous Occult Papillary Thyroid Microcarcinoma 
Yonsei Medical Journal  2010;51(4):609-611.
This is a case report on papillary thyroglossal duct cyst (TGDC) carcinoma along with synchronous occult papillary thyroid microcarcinoma. A 46-year-old woman visited our hospital because she had an anterior midline neck mass below her hyoid bone. Preoperative ultrasound-guided fine-needle aspiration cytology revealed signs of papillary TGDC carcinoma. We performed a Sistrunk operation and a total thyroidectomy. Histopathological examination of the specimen revealed papillary carcinoma arising in the TGDC and papillary microcarcinoma of the thyroid gland without extrathyroidal extension. Surgeons should be aware of TGDC carcinoma during surgical planning and postoperative treatment and should differentiate this carcinoma from an anterior midline neck mass.
doi:10.3349/ymj.2010.51.4.609
PMCID: PMC2880280  PMID: 20499433
Thyroglossal duct cyst carcinoma; synchronous; occult; thyroid microcarcinoma
21.  Molecular prognostic factors in rectal cancer treated by preoperative chemoradiotherapy 
Oncology Letters  2010;1(1):23-29.
The present study evaluated the expression of p53, pRb, hMLH1 and MDM2 prior to preoperative chemoradiotherapy (CRT) in patients with rectal cancer, and attempted to determine any correlation with treatment outcome. Forty-five patients with available pretreatment biopsy tissues and who received preoperative CRT were enrolled in this study. Preoperative CRT consisted of a median 50.4 Gy and 2 cycles of concurrent administration of 5-fluorouracil + leucovorin. Surgery was performed approximately seven weeks after CRT. Protein expression in formalin-fixed paraffin-embedded biopsy specimens was assessed by immunohistochemistry. A positive expression of p53, pRb, hMLH1 and MDM2 was found in 40, 46.7, 40 and 66.7% of the tissue specimens, respectively. The 5-year overall (OS), disease-free (DFS) and locoregional recurrence-free survival (LRFS) rates for patients included in the study were 71.3, 66.1 and 60.9%, respectively. p53 expression presented a significantly different OS (positive vs. negative, 45.8 vs. 86.2%; p=0.02). However, the expression of pRb, hMLH1 and MDM2 was not significant for OS. The expression of p53 was a borderline significant prognostic factor for DFS and for LRFS. Age, p53 and MDM2 expression were significant factors in the multivariate analysis performed for OS with 12 covariates, including 8 clinicopathological parameters and 4 proteins. No significant factor affected DFS or LRFS in the multivariate analysis. We suggest that the expression of p53 is a potential marker of survival. Determinations of this protein expression may be useful for selecting candidates from rectal cancer patients for more tailored treatment.
doi:10.3892/ol_00000004
PMCID: PMC3436461  PMID: 22966250
rectal neoplasms; preoperative chemoradiotherapy; p53; pRb; hMLH1; MDM2
22.  Microsatellite instability at a tetranucleotide repeat in type I endometrial carcinoma 
Background
Microsatellite instability (MSI) at tri- or tetranucleotide repeat markers (elevated microsatellite alterations at selected tetranucleotide repeat, EMAST) has been recently described. But, the underlying genetic mechanism of EMAST is unclear. This study was to investigate the prevalence of EMAST, in type I endometrial carcinoma, and to determine the correlation between the MSI status and mismatch repair genes (MMR) or p53.
Methods
We examined the 3 mono-, 3 di-, and 6 tetranucleotide repeat markers by PCR in 39 cases of type I endometrial carcinoma and performed the immunohistochemistry of hMSH2, hMLH1, and p53 protein.
Results
More than two MSI at mono- and dinucleotide repeat markers was noted in 8 cases (MSI-H, 20.5%). MSI, at a tetranucleotide repeat, was detected in 15 cases (EMAST, 38.5%). In remaining 16 cases, any MSI was not observed. (MSS, 42.1%), MSI status was not associated with FIGO stage, grade or depth of invasion. The absence of expression of either one of both hMSH2 or hMLH1 was noted in seven (87.5%) of eight MSI-H tumors, one (6.3%) of 16 MSS tumors, and five (33.3%) of 15 EMAST tumors. (p = 0.010) The expression of p53 protein was found in one (12.5%) of eight MSI-H tumors, five (31.3%) of 16 MSS tumors, and seven of 15 EMAST tumors. (p = 0.247)
Conclusion
Our results showed that about 38.5% of type I endometrial carcinomas exhibited EMAST, and that EMAST was rarely associated with alteration of hMSH2 or hMLH1.
doi:10.1186/1756-9966-27-88
PMCID: PMC2637840  PMID: 19116039
23.  Hepatocellular Carcinoma Presenting as Uterine Metastasis 
Metastatic extragenital cancer that spreads to the uterus is rare. When it occurs, the extragenital primary disease is often in the breast or gastrointestinal tract. We report here on a case of hepatocellular carcinoma (HCC) that metastasis to the uterus. The patient was admitted for evaluation of a pelvic mass. The serum alpha-fetoprotein level was highly elevated. Magnetic resonance imaging of the abdomen and pelvis showed hepatic and uterine masses. The patient underwent surgical treatment. The histopathologic findings and immunohistochemical staining results of the uterine mass were char acteristics of metastatic HCC. The endometrium and both ovaries were free of tumor. Up to now, there have been only two cases of uterine metastasis from HCC reported in the English literature. This case is the first documented instance of a metastatic uterine tumor from HCC that spared both ovaries.
doi:10.4143/crt.2008.40.3.141
PMCID: PMC2697462  PMID: 19688121
Hepatocellular carcinoma; Uterine metastasis; Uterine neoplasm
24.  Primary Epithelial Ovarian Carcinoma with Gastric Metastasis Mimic Gastrointestinal Stromal Tumor 
Epithelial ovarian carcinoma rarely metastasizes to the parenchyma of the stomach. A 55-years-old woman presented with epigastric pain and a feeling of fullness for one month. A subsequent contrast-enhanced CT scan demonstrated a 4.5×4 cm submucosal mass with focal ulceration in the gastric antrum, and this finding was suggestive of GIST. After gastric antrectomy, the final pathology showed metastatic gastric tumor from a primary ovarian serous carcinoma. Because epithelial ovarian carcinoma is usually spread along the peritoneal surface, stomach involvement is rare. Furthermore, transmural gastric metastasis is very rare in a patient with primary ovarian carcinoma. Until now, there has been no reported case of stomach involvement at presentation in a patient with primary ovarian carcinoma. We present here a case of ovarian carcinoma with gastric metastasis that mimicked GIST.
doi:10.4143/crt.2008.40.2.93
PMCID: PMC2697489  PMID: 19688055
Gastric metastasis; Gastrointestinal stromal tumors; Ovarian carcinoma
25.  Mesenteric extraskeletal osteosarcoma with telangiectatic features: a case report 
BMC Cancer  2007;7:82.
Background
Extraskeletal osteosarcoma is a rare malignant mesenchymal tumor, with a predominant occurrence in the extremities. Only two cases of mesenteric extraskeletal osteosarcoma have been documented. We describe an unusual case of extraskeletal osteosarcoma with telangiectatic features occurring in the mesentery.
Case presentation
A 67-year-old male presented with blood-tinged stool of 1-month's duration. On colonoscopy, a solid mass was detected protruding from the colon wall. Computed tomography showed a 15 × 9.7 cm heterogeneously enhancing mass, with mottled calcification and a cystic portion, occupying the left upper quadrant of the abdominal cavity. Curative resection of the tumor was performed, and the excised tumor was composed of large multilocular cysts containing old hematomas and necrotic debris. The histology revealed an osteosarcoma showing osteoid formation and blood-filled spaces lined with atypical cells. Despite postoperative chemotherapy, he developed a recurrent peritoneal mass and multiple lung metastases 3 months postoperatively.
Conclusion
Given the rarity of cases of mesenteric extraskeletal osteosarcoma, its biologic behavior at this location remains to be determined. However, extraskeletal osteosarcoma with telangiectatic features is an uncommon entity to be recognized because of the possible fatal outcome related to the tumors.
doi:10.1186/1471-2407-7-82
PMCID: PMC1878495  PMID: 17504524

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