Sung Sun Kim

Expression of matrix metalloproteinases and their inhibitors in different immunohistochemical-based molecular subtypes of breast cancer

BackgroundMetalloproteinases (MMPs) and their tissue inhibitors of metalloproteinases (TIMPs) are involved in several key pathways of tumor growth, invasion and metastasis, but little is known about their expression according to different molecular subtypes of breast cancer. The aims of this study were to assess the prevalence and clinical significance of MMP and TIMP expression in invasive breast cancer and to determine its association with immunohistochemical-based molecular classification.MethodsTissue microarray sections were immunostained for estrogen receptor-α (ER-α), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), cytokeratin (CK) 5/6, epidermal growth factor receptor (EGFR) and with specific antibodies against MMP-1, 2, 7, 9, 11, 13, and 14 and TIMP-1, 2, and 3. Based on the immunostaining data from five of the markers used (ER-α, PR, HER2, EGFR and CK5/6), three major subtypes (123 luminal A, 31 basal-like, and 17 HER2-overexpressing) were selected.ResultsStatistically significant differences in the expression of MMPs and TIMPs among the three subtypes were found in tumoral MMP7 (P = 0.005), tumoral MMP-9 (P = 0.000), tumoral MMP-13 (P = 0.016) and stromal MMP-13 (P = 0.016). The incidence of tumoral MMP-9 expression in the HER2-overexpressing subtype was significantly higher than in the luminal A subtype (P = 0.021). Tumoral MMP-9 and stromal MMP-13 expression were significantly higher in the HER2-overexpressing subtype than in the basal-like subtype (P = 0.000 and P = 0.016, respectively). Tumoral MMP-7 expression was significantly higher in the basal-like subtype compared to luminal A (P = 0.007) and HER2-overexpressing subtype (P = 0.004). Tumoral MMP-13 showed a higher expression in the basal-like subtype than in the HER2-overexpressing subtype (P = 0.010). In multivariate analysis, stage and stromal MMP-1 expression were significantly related to overall survival. Stage was of independent prognostic significance for disease-free survival.ConclusionWe found some variations in MMP and TIMP expression among the immunohistochemical-based molecular subtypes of breast carcinomas, suggesting differences in their tumor pathophysiology. Additional studies are needed to determine the mechanisms underlying the differences of MMP and TIMP expression in the molecular subtypes for the development of specific therapeutic targets for breast cancer subtypes.

Cytologic features of primary signet ring cell carcinoma of the bladder: a case report.

BACKGROUND Signet ring cell carcinoma is a very rare subtype of adenocarcinoma of the urinary bladder. Urine cytology is a useful method for screening and followup of urinary bladder carcinoma. CASE A 43-year-old woman was referred for evaluation of painless hematuria. Laboratory evaluation showed anemia, hematuria and elevated tumor marker levels. Pelvic computed tomography (CT) demonstrated diffuse wall thickening, and the chest CT suggested metastatic lesions in the lung and hepatic dome. Abdominal CT, esophagogastroduodenoscopy and colonoscopy revealed no evidence of malignancy in the gastrointestinal tract. Cystoscopy revealed very large masses in the anterior and posterior wall of the bladder. Bladder washings, urine cytology and biopsy demonstrated characteristic signet ring cells without foci of urothelial carcinoma or other lesions. Three months later, ascitic fluid was obtained; the results showed signet ring cells identical to those seen in the urine specimen. CONCLUSION Signet ring cell carcinoma of the urinary bladder can be diagnosed by urinary cytology and confirmed by cystoscopic biopsy.

Microscopic and nuclear morphometric findings of chromophobe renal cell carcinoma, renal oncocytoma, and tumor with overlapping histology☆

We compared the microscopic and nuclear morphometric characteristics of classical chromophobe renal cell carcinoma (C-ChRC) and renal oncocytoma (RO) and applied meaningful characteristics to differentiate eosinophilic chromophobe renal cell carcinoma (E-ChRC) from RO that has overlapping histology (RO-OH) with E-ChRC to know the usefulness of nuclear morphometry. Microscopic and morphometric characteristics were evaluated in 24 C-ChRCs, 6 E-ChRCs, 5 RO-OHs, and 25 classical ROs (C-ROs). The microscopic findings favoring C-ChRC were rasinoid nuclei, perinuclear halo, and distinct cytoplasmic membrane. Characteristic for C-RO was either stromal edema or hyalinization. The morphometric values of nearest nuclear distance, shortest nuclear diameter, and nuclear diameter ratio were significantly different between C-ChRC and C-RO. However, it was impossible to distinguish E-ChRC from RO-OH by histology and nuclear morphometry. The results of our study show that nuclear morphometry and histomorphology can distinguish between C-ChRC and C-RO but not between E-ChRC and RO-OH.

Peritoneal Melanosis Associated With Mucinous Cystadenoma of the Ovary and Adenocarcinoma of the Colon

Peritoneal melanosis, a diffuse, black pigmentation of the peritoneum, is a very rare condition characterized by melanin pigment deposition in the peritoneum. In this paper, we describe a case of peritoneal melanosis associated with a mucinous cystadenoma on an ovary and adenocarcinoma in the colon of 68-year-old women. The patient was referred for an evaluation of lower abdominal pain and distension. Laboratory results showed anemia and elevated CA 125 levels. A pelvic computed tomographic scan revealed a huge multicystic mass on the right ovary and a well-enhancing intraluminal mass located at the rectosigmoid junction. During a surgical procedure, India-ink-colored (black) pigmentation was seen in the peritoneum, in the omentum, and on the surface of the ovary. Biopsies of the omentum and peritoneum showed pigment in the stroma and pigment-laden histiocytic aggregation. Pigment was also present in the wall of the mucinous cystadenoma of the ovary and colonic serosa. An ultrastructural study found melanosome in the cytoplasm of the histiocytes.

Mesonephric Adenocarcinoma of the Uterine Corpus: A Case Report and Diagnostic Pitfall.

Mesonephric adenocarcinoma is a rare tumor type that is usually found in areas where the Wolffian duct was present during the fetal period. We report a case of mesonephric adenocarcinoma of the uterine corpus in a 66-year-old woman who presented with vaginal bleeding. Pelvic magnetic resonance imaging revealed a 2.7-cm-sized irregular thickening and enhancement of the uterine body. The diagnosis following endometrial curettage biopsy was endometrioid adenocarcinoma, and the patient underwent a total hysterectomy with bilateral salpingo-oophorectomy. The tumor was composed of small tubular and ductal components, and a retiform appearance was also observed in the deeper areas. The tumor cells were immunopositive for cytokeratin, vimentin, CD10 with a luminal staining pattern, PAX2, and PAX8, and immunonegative for estrogen receptor and progesterone receptor, which was consistent with tumor of mesonephric origin. Mesonephric neoplasms reveal relatively low-grade nuclear feature, characteristic immunoprofiles (immunonegative for ER and PR, and immunopositive for CD10, PAX2, PAX8, and GATA3), and unique tumor location (myometrium), whereas Müllerian neoplasms such as endometrial adenocarcinoma show various morphology, immunopositivity for ER and PR, and primarily endometrial location. As described above, an integration of the clinical features, morphologic characteristics, and immunohistochemical profiles is needed to make a diagnosis.

Metastatic Pulmonary Ameloblastoma Misdiagnosed as Primary Squamous Cell Carcinoma Preoperatively

Ameloblastomas are rare odontogenic epithelial tumors that occur mainly in the mandible. Despite their benign histologic appearance, they are locally aggressive with a high recurrence rate. However, a metastasizing ameloblastoma has been rarely reported. According to the current World Health Organization classification system, the definitive diagnosis of metastasizing ameloblastoma can only be carried out in retrospect, after the event of metastasis. This case report describes a patient with metastatic pulmonary ameloblastoma, 17 years after the surgical excision of an odontogenic tumor, preoperatively misdiagnosed as primary squamous cell carcinoma.

Cytokeratin-positive gastrointestinal stromal tumor of biphasic morphology: a case report.

Gastrointestinal stromal tumor (GIST), which is associated with mutations in KIT or a platelet-derived growth factor receptor, alpha polypeptide (PDGFRA), is the most common mesenchymal tumor of the gastrointestinal tract[1]. A definitive diagnosis of GIST is important to ensure administration of effective drugs, such as imatinib mesylate, and immmunohistochemical staining for c-Kit or DOG1 is useful for the diagnosis. According to previous studies, cytokeratin (CK) expression is a rare event in GISTs[2-6], so they can easily be misdiagnosed as other epithelial or epithelioid mesenchymal tumors. In such cases, a diagnosis of GIST can be made when DOG1 immunoreactivity or mutation of KIT or PDGFRA are observed.

Yes-Associated Protein Expression Is Correlated to the Differentiation of Prostate Adenocarcinoma

Background Yes-associated protein (YAP) in the Hippo signaling pathway is a growth control pathway that regulates cell proliferation and stem cell functions. Abnormal regulation of YAP was reported in human cancers including liver, lung, breast, skin, colon, and ovarian cancer. However, the function of YAP is not known in prostate adenocarcinoma. The purpose of this study was to investigate the role of YAP in tumorigenesis, differentiation, and prognosis of prostate adenocarcinoma. Methods The nuclear and cytoplasmic expression of YAP was examined in 188 cases of prostate adenocarcinoma using immunohistochemistry. YAP expression levels were evaluated in the nucleus and cytoplasm of the prostate adenocarcinoma and the adjacent normal prostate tissue. The presence of immunopositive tumor cells was evaluated and interpreted in comparison with the patients’ clinicopathologic data. Results YAP expression levels were not significantly different between normal epithelial cells and prostate adenocarcinoma. However, YAP expression level was significantly higher in carcinomas with a high Gleason grades (8–10) than in carcinomas with a low Gleason grades (6–7) (p < .01). There was no statistical correlation between YAP expression and stage, age, prostate-specific antigen level, and tumor volume. Biochemical recurrence (BCR)–free survival was significantly lower in patients with high YAP expressing cancers (p = .02). However high YAP expression was not an independent prognostic factor for BCR in the Cox proportional hazards model. Conclusions The results suggested that YAP is not associated with prostate adenocarcinoma development, but it may be associated with the differentiation of the adenocarcinoma. YAP was not associated with BCR.

Carcinoid tumor associated with adjacent dysplastic columnar epithelium in the renal pelvis: A case report and literature review.

Carcinoid tumors are well documented in the pulmonary and gastrointestinal systems, but very rare in the urinary tract, especially in the renal pelvis. We report on a 60‐year‐old female patient who presented with left flank pain and fever. Abdominal computed tomography demonstrated a heterogeneously enhancing mass in the left renal pelvis and a stone at the left proximal ureter. Multiple parenchymal lesions were also observed, which were identified as uneven caliectasis displaying air‐fluid levels and renal parenchymal atrophy. The patient underwent simple nephro‐ureterectomy. Macroscopically, a polypoid mass was observed in the renal pelvis. Microscopically, the tumor revealed acinar, tubular, and solid pattern and was composed of small, monotonous and hyperchromatic cells. Lining epithelia in renal pelvis and ureter revealed columnar epithelia with dysplastic change. The tumor cells were positive for chromogranin A, synaptophysin, CD56, and focally positive for cytokeratin. Immunohistochemical staining of synaptophysin and chromogranin A highlighted the neuroendocrine cells in the columnar epithelium. Ki‐67 (1:50; MIB‐1) labeling index was less than 1% in the area with highest uptake. We report here a case of carcinoid tumor of the renal pelvis that was associated with adjacent dysplastic columnar epithelium.

Hybrid granular cell tumor/perineurioma.

Hybrid peripheral nerve sheath tumors (PNSTs), which show hybrid features of more than one cell type normally found in a peripheral nerve sheath, are recently recognized clinical entities. Various composite tumors have been reported; however, granular cell tumor/perineurioma is a rare combination [1-4]. Since perineurial cells may be found in other types of PNSTs, it is important to determine if those are reactive, remnantal, or true neoplastic when a perineurial component of the PNST is identified. Main differential diagnoses include granular perineurioma and granular cell tumor with reactive perineurial cell hyperplasia, which show a lack of immunopositivity for S-100 in the granular cells and prominent perineurial cell proliferation throughout the tumor, respectively.