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The author reports a rare case of sarcomatoid carcinoma with an emphasis on immunohistochemical features. A 79-year-old man was admitted to our hospital because of hematuria. An endoscopy revealed a large polypoid tumor in the bladder, and urine cytology demonstrated malignant cells. A cystectomy was performed. The patient is now alive without metastasis 4 months after the operation. Grossly, a large polypoid tumor (5 x 6 x 5 cm) was present in the bladder. Microscopically, the tumor consisted of high-grade transitional cell carcinoma element (10% in area) and sarcomatoid element (90% in area). There was a gradual transition between the two. The tumor cells were invaded into peribladder tissue (pT3b). Immunohistochemically, the sarcomatoid element was positive for four types of pancytokeratins, high-molecular weight cytokeratin (CK), CK5/6, CK7, CK18, CK19, epithelial membrane antigen (EMA), vimentin, p53 protein, p63, Ki-67 (labeling = 92%), neuron-specific enolase (NSE), and platelet-derived growth factor receptor-alpha (PDGFRA). It was negative for CK14, CK20, melanosome, carcinoembryonic antigen (CEA), desmin, S100 protein, myoglobin, alpha-smooth muscle antigen (ASMA), CD34, chromogranin, synaptophysin, CD56, CD68, and KIT. The transitional cell carcinoma element showed similar immunoreactivity except for negative CK5/6, positive CK20, and negative vimentin. A molecular genetic analysis of KIT gene (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) gene with the use of PCR-direct sequencing showed no mutations. The present case is the first report of sarcomatoid carcinoma of the urinary bladder demonstrating extensive immunohistochemistry and mutational status of KIT and PDGFRA genes. The sarcomatoid carcinoma in the present case may be derived from sarcomatous differentiation of high-grade transitional cell carcinoma.
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PMID:Sarcomatoid carcinoma of the urinary bladder: a case report with immunohistochemical and molecular genetic analysis. 1952 96

The author reports a very rare case of cutaneous metastasis of sarcomatoid carcinoma of the lung. The skin metastasis was an initial presentation. A 67-year-old man consulted our hospital because of left chest skin mass. An excisional biopsy was performed, and it showed proliferation of malignant sarcomatoid spindle and polygonal cells in the deep dermis and subcutis remote from the epidermis and appendages. Immunohistochemically, the tumor cells were positive for pancytokeratins, cytokeratin (CK) 7, CK 18, vimentin, p53, Ki-67 (95%) and PDGFRA. They were negative for high molecular weight CK, CK 5/6, CK 14, CK 19, CK 20, epithelial membrane antigen, TTF-1, CEA, desmin, S100 protein, alpha-smooth muscle actin, p63, CD34, surfactant apoprotein A, chromogranin, synaptophysin, neuron-specific enolase, CD68, CD56, D2-40, calretinin and KIT. A pathological diagnosis of metastatic sarcomatoid carcinoma probably originating from the lung was made. Then, the patient was admitted to our hospital, and imaging modalities including computed tomography (CT) and magnetic resonance imaging (MRI) revealed a tumor in the left lung. No other tumors were detected in the imaging techniques. Lung biopsy was planned, but the patient suddenly died; the cause of death was unclear. Autopsy was not performed. The present report suggests that sarcomatoid carcinoma of the lung should be considered in cutaneous metastatic lesions.
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PMID:Sarcomatoid carcinoma of the lung presenting as a cutaneous metastasis. 1960 61

Breast cancers of basal phenotype have been identified by molecular profiling and are associated with a poor prognosis. This review describes the morphological characteristics of these tumors and focuses on their profiling using immunohistochemistry: absence of detectable hormone receptors and HER2, expression of basal cytokeratins (CK5/6, CK14), myoepithelial markers (p63, smooth muscle actin) and HER1. This phenotype may be encountered in all histological types of breast cancer and is further divided into three subtypes according to prognosis and protein profiling. Pure basal and basal/myoepithelial subtypes have a poor prognosis in contrast to the myoepithelial subtype.
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PMID:[Basal-like breast cancer: a review]. 1961 22

We report 2 cases of a distinctive neoplasm arising from Bartholin gland and presenting as a vulval or vaginal mass. The tumors occurred in patients aged 44 and 51 years and were 2 and 3 cm in maximum dimension. In both cases, normal Bartholin gland tissue was identified adjacent to the lesion. The neoplasms were unencapsulated and largely well circumscribed but with a focally infiltrative edge. They were composed of tubular, trabecular, or insular arrangements with a double layer of inner cuboidal cells with round nuclei and outer cells with ovoid nuclei and clear cytoplasm, corresponding to epithelial and myoepithelial cells, respectively. Luminal eosinophilic colloid-like material was present. In both cases, a minor proportion of the neoplasm consisted of cribriform arrangements, creating an appearance reminiscent of adenoid cystic carcinoma, although the overall morphology was not typical of that lesion. Mitotic figures were identified in both cases, the mitotic count being 1 and 5/10 high-power fields. Immunohistochemically, the inner cells were positive with epithelial markers, including broad-spectrum cytokeratins and epithelial membrane antigen, and the outer cell layer was positive with myoepithelial markers p63, calponin, and alpha-smooth muscle actin. Both neoplasms exhibited diffuse strong immunoreactivity of the epithelial cells with c-kit. Activating mutations in KIT exons 9, 11, 13, and 17 and in platelet-derived growth factor receptor alpha exons 12, 14, and 18 were searched for by polymerase chain reaction and direct sequencing but were not identified. We believe this represents a low-grade carcinoma arising from Bartholin gland composed of a dual population of epithelial and myoepithelial cells and closely resembling the salivary gland neoplasm termed epithelial-myoepithelial carcinoma. We propose the term low-grade epithelial-myoepithelial carcinoma of Bartholin gland.
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PMID:Low-grade epithelial-myoepithelial carcinoma of bartholin gland: report of 2 cases of a distinctive neoplasm arising in the vulvovaginal region. 1962 Sep 48

Canine Merkel cell tumours are rare neuroendocrine neoplasms that show a relatively benign biological behaviour when compared with their human counterparts. To date, little information is available on their immunohistochemical properties. This report describes the histopathological and immunohistochemical features of two such tumours. The tumours' immunoreactivity profile was studied with respect to different cellular molecules including chromogranin A (CGA), neurone-specific enolase (NSE), S100 protein, c-KIT, the cytokeratins (CKs) detected by pancytokeratin (AE1/AE3) antibodies (i.e. high molecular weight CKs 1, 2, 3, 4, 5, 6, 10, 14, 15 and 16, and low molecular weight CKs 7, 8 and 19) and three markers proposed to correlate with increased malignancy in human tumours: E-cadherin, beta-catenin and p63 protein. In both lesions, tumour cells were positive for cytokeratins, CGA, NSE, S100 and c-KIT. No immunostaining was observed for p63 protein, and there was no loss or change in E-cadherin or beta-catenin immunoexpression. These results suggest that the generally benign behaviour of canine Merkel cell tumours, when compared with their human counterparts, may be partly explained by the conservation of important intercellular adhesion molecules such as E-cadherin and beta-catenin. Additionally, expression of S100 but not of the p63 protein suggests that these canine tumours present a trend towards neural, rather than basal, epithelial differentiation and do not readily compare with human Merkel cell tumours.
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PMID:Two canine Merkel cell tumours: immunoexpression of c-KIT, E-cadherin, beta-catenin and S100 protein. 1970 8

This report describes 3 cases of a distinctive, hitherto unreported gastric epitheliomesenchymal biphasic tumor that differs from other biphasic tumors of the stomach and elsewhere: carcinosarcoma, biphasic synovial sarcoma, teratoma, and mixed tumor. The tumors occurred in young adults, 2 males and 1 female, of ages 19, 27, and 30 years. Two tumors were located in the greater curvature in the gastric body and one in the antrum. The tumors measured 5, 6, and 15 cm in maximum diameter, and their mitotic rates were 0, 4, and 30 mitoses per 50HPF. There were 2 components: uniform oval or spindled cells in diffuse sheets, and clusters or cords of epithelial cells occasionally forming glandular structures with small lumens. The epithelial elements were positive for keratin cocktail AE1/AE3, keratin 18, and partly for keratin 7, but were negative for keratins 5/6, 20 and epithelial membrane antigen. The spindle cells were positive for vimentin and CD10. All components were negative for CD34, CD99, estrogen receptor, KIT, smooth muscle actin, desmin S100 protein, p63, calretinin, chromogranin, synaptophysin, CDX2, and thyroid transcription factor 1. In situ hybridization for SS18 rearrangement was negative in all cases separating this tumor from synovial sarcoma. All 3 patients were alive after follow-up of 3.5, 5, and 14 years. Because these tumors have some resemblance to blastomas of other organs, we propose the term "gastroblastoma" for this distinctive, at least low-grade malignant epitheliomesenchymal tumor of the stomach.
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PMID:A distinctive novel epitheliomesenchymal biphasic tumor of the stomach in young adults ("gastroblastoma"): a series of 3 cases. 1971 90

Human anal canal squamous cell carcinoma (SCC) cell line has not yet been reported due to the rarity of this disease. Since cell lines to study this malignancy were not available, we attempted to establish and characterize anal canal SCC cell line from primary culture of lymph node metastasis. Six sublines were cloned and isolated from parental cells. They were designated as SaTM-1A, B, C, D, E and F. The features of the six sublines were characterized by reverse transcription-PCR, chemosensitivity test to 5-Fu and CDDP, immunohistochemistry, cDNA microarray analysis and tumorigenicity using immunodeficient mice. All sublines were proliferated in multiple layers at an average doubling time of 24.5 h. VEGF-A, -B, VEGFR-1, -R3 and EGFR were expressed in all sublines, whereas VEGF-D and EGF were not detected in all. SaTM-1 was proven to retain the characteristics of SCC by detection of p63 and cytokeratin 5/6. The cytotoxic effects of 5-Fu were almost similar, although those of CDDP showed different behavior, which was divided into two groups (SaTM-1A, B, E and SaTM-1C, D, F). The differences in gene expression between two groups were analyzed according to susceptibility to cytotoxic effects of CDDP. Thirty-six genes were successfully identified, which may be potentially associated with CDDP resistance. SaTM-1 cells formed tumors easily in vivo, therefore all subclones had tumorigenic property. This is the first report of successful establishment and characterization of a human anal canal SCC cell line, which may provide beneficial resources for investigating the biological features of human anal canal SCC.
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PMID:Establishment and characterization of the human SaTM-1 anal canal squamous cell carcinoma cell line derived from lymph node metastasis. 1972 86

Approximately 10 - 15% of breast carcinomas (BCs) are known to be 'triple-negative (TN) receptor' (i.e., not expressing ER or PR and not exhibiting overexpression and/or gene amplification of HER2-neu). Triple-negative BCs comprise approximately 85% of all basal-type tumours. Classically, basal-like BCs have been characterised by low expression of ER, PR, and HER2 neu and high expression of CK5, CK14, caveolin-1, CAIX, p63, and EGFR (HER1), which reflects the mammary gland basal/myoepithelial cell component. Although there is no standard first-line chemotherapy regimen for metastatic TN BCs, anthracycline- and taxane-containing regimens are acceptable treatments. A large number of agents, including DNA-damaging agents, EGFR inhibitors, antiangiogenic agents and novel taxane formulations are currently being tested in clinical trials for first-line and pretreated patients. Limited experiences with platinum salts, poly(ADP-ribose) polymerase (PARP) inhibitors, cetuximab, bevacizumab and ixabepilone have been published in recent years and will be reported. Novel immunohistochemistry analysis for identification of basal like/TN phenotype are awaited to correctly select this population. The clinical trials investigating new agents have to be designed for a specific (and possibly large) subset of patients with BC. In the future, a gene array platform with greater sensitivity for distinguishing the various BC subtypes, as well as having the power to predict the molecular biology of the disease, will be an indispensible tool for treatment selection. Currently, treatment of TN BC is more empirical than evidence-based. The cornerstone of treatment is chemotherapy, but in the near future, novel target agents will emerge as possible partners.
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PMID:Current data of targeted therapies for the treatment of triple-negative advanced breast cancer: empiricism or evidence-based? 1973 14

The author reports herein a case of occult very small lung carcinoma with a solitary brain metastasis that is clinically diagnosed as cavernous hemangioma, with an emphasis on pathologic findings. A 48-year-old Japanese man was admitted to our hospital complaining of mild paresis of left leg. Brain CT and MRI showed a solitary tumor (2 cm) with features of cavernous hemangioma in the right temporal lobe. Tumorectomy was performed, and it was pathologically undifferentiated carcinoma. An immunohistochemical analysis reveled that the carcinoma cells were positive for four types of pancytokeratin, cytokeratin (CK) 5/6, CK7, CK18, CK19, p63, and Ki-67 (78%). They were negative for high molecular weight CK, CK14, CK20, TTF-1, PE-10, melanosome, S100 protein, EMA, vimentin, CD34, myoglobin, CEA, p53, desmin, alpha-smooth muscle actin, chromogranin, synaptophysin, CD56, neuron-specific enolase, CD68, KIT, and PDGFRA. The positive CK7 and negative CK20 suggested lung origin, and cytokeratin profiles and positive CK5/6 and p63 suggested a squamous differentiation. The pathological diagnosis was undifferentiated carcinoma with squamous differentiation probably of lung origin. Later, systemic CT, MRI and PET were performed, and they detected a small lung tumor (8 mm) in the right apex. The lung biopsy revealed an undifferentiated carcinoma with focal squamous differentiation; the immunohistochemical findings were the same as those of the brain tumor. These findings suggest that occult very small lung carcinoma can metastasize to brain and such a metastasis may mimic cavernous hemangioma radiologically. Pathologic observations using many antibodies are very useful to determine the origin and histological type in solitary brain nodule.
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PMID:Occult very small lung carcinoma with a solitary brain metastasis that is clinically diagnosed as cavernous hemangioma: a case report. 1982 73

Scutellaria baicalensis is an anti-inflammatory and antineoplastic Chinese herbal therapy. We have previously shown that S. baicalensis can inhibit hepatocellular carcinoma (HCC) cell growth in vitro. In this study, we sought to determine the effect of S. baicalensis on the cell signaling network using our newly developed Pathway Array technology, which screens cell signaling pathways involved in cell cycle regulation. The HCC cell line (HepG2) was treated with S. baicalensis extract in vitro. The effect on the cell cycle was analyzed by flow cytometry, and the expression of various signaling proteins was assayed with Pathway Array. Our results indicate that S. baicalensis exerts a strong growth inhibition of the HepG2 cells via G(2)/M phase arrest. The Pathway Array analysis of 56 proteins revealed a total of 14 differentially expressed proteins or phosphorylations after treatment. Of these, 9 showed a dose-dependent decrease (p53, ETS1, Cdc25B, p63, EGFR, ERK1/2, XIAP, HIF-2alpha, and Cdc25C) whereas one demonstrated a dose-dependent increase (Cyclin E) after treatment with 200 microg/ml of S. baicalensis. Using computer simulation software, we identified additional hubs in the signaling network activated by S. baicalensis. These results indicate that S. baicalensis exerts a broad effect on cell signaling networks leading to a collective inhibition of cell proliferation.
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PMID:The effect of Scutellaria baicalensis on the signaling network in hepatocellular carcinoma cells. 1983 25


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