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NOTCH2 expression is decreased in epithelial ovarian cancer and is related to the tumor histological subtype.

ABSTRACT: BACKGROUND:Notch family members function as both oncogenes and tumor suppressors. NOTCH2 is down-regulated in colon cancer, and reduced expression is associated with a less differentiated, more aggressive phenotype, and reduced overall survival. NOTCH2 has also been shown to have pro-apoptotic and growth suppressive effects in thyroid carcinoma, and carcinoid tumors. The expression pattern of NOTCH2 in ovarian cancer is unknown. METHODS:An immunohistochemical analysis using a polyclonal antibody to the NOTCH2 intracellular domain was performed on a total of 119 ovarian carcinomas, and 7 serous borderline tumors, arranged onto tissue arrays. Normal ovarian and fallopian tube epithelium were used as controls. Specimens were scored as low or high NOTCH2 expression. The score distributions for the subtypes were analyzed with the chi square test. RESULTS:Fifty two of 61 (85.2%) papillary serous, eight of 13 (61.5%) clear cell, and 23 of 30 (76.7%) endometrioid, demonstrated negative or lower NOTCH2 expression than normal fallopian tubal epithelium or ovarian surface epithelium. In contrast, 10 of 15 (66.7%) mucinous carcinomas had a high level of NOTCH2 expression and consistently demonstrated intense polarized staining (P<.001). The apical expression of NOTCH2 protein present in the normal fallopian tube epithelium and many borderline tumors was absent in the high grade carcinomas, most notably in papillary serous. CONCLUSION:Decreased NOTCH2 expression is associated with the poorly differentiated serous epithelial ovarian carcinoma histology. Further studies are needed to assess the functional role of NOTCH2 in ovarian cancer and its effect on prognosis.

SUBMITTER: Galic V

PROVIDER: S-EPMC3975618 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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<i>NOTCH2</i> expression is decreased in epithelial ovarian cancer and is related to the tumor histological subtype.

Galic Vijaya V Shawber Carrie J CJ Reeves Claire C Shah Monjri M Murtomaki Aino A Wright Jason J Herzog Thomas T Tong Guo Xia GX Kitajewski Jan J

Pathology discovery 20130801

<h4>Background</h4>Notch family members function as both oncogenes and tumor suppressors. <i>NOTCH2</i> is down-regulated in colon cancer, and reduced expression is associated with a less differentiated, more aggressive phenotype, and reduced overall survival. <i>NOTCH2</i> has also been shown to have pro-apoptotic and growth suppressive effects in thyroid carcinoma, and carcinoid tumors. The expression pattern of <i>NOTCH2</i> in ovarian cancer is unknown.<h4>Methods</h4>An immunohistochemical ...[more]

PMID: 24707357

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Project description:Previous studies have implicated vestigial like 3 (VGLL3), a chromosome 3p12.3 gene that encodes a putative transcription co-factor, as a candidate tumor suppressor gene (TSG) in high-grade serous ovarian carcinomas (HGSC), the most common type of epithelial ovarian cancer. A complementation analysis based on microcell-mediated chromosome transfer (MMCT) using a centric fragment of chromosome 3 (der3p12-q12.1) into the OV-90 ovarian cancer cell line haploinsufficient for 3p and lacking VGLL3 expression was performed to assess the effect on tumorigenic potential and growth characteristics. Genetic characterization of the derived MMCT hybrids revealed that only the hybrid that contained an intact VGLL3 locus exhibited alterations of tumorigenic potential in a nude mouse xenograft model and various in vitro growth characteristics. Only stable OV-90 transfectant clones expressing low levels of VGLL3 were derived. These clones exhibited an altered cytoplasmic morphology characterized by numerous single membrane bound multivesicular-bodies (MVB) that were not attributed to autophagy. Overexpression of VGLL3 in OV-90 was achieved using a lentivirus-based tetracycline inducible gene expression system, which also resulted in MVB formation in the infected cell population. Though there was no significant differences in various in vitro and in vivo growth characteristics in a comparison of VGLL3-expressing clones with empty vector transfectant controls, loss of VGLL3 expression was observed in tumors derived from mouse xenograft models. VGLL3 gene and protein expression was significantly reduced in HGSC samples (>98%, p < 0.05) relative to either normal ovarian surface epithelial cells or epithelial cells of the fallopian tube, possible tissues of origin of HGSC. Also, there appeared to be to be more cases with higher staining levels in stromal tissue component from HGSC cases that had a prolonged disease-free survival. The results taken together suggest that VGLL3 is involved in tumor suppressor pathways, a feature that is characterized by the absence of VGLL3 expression in HGSC samples.

Dataset Information

NOTCH2 expression is decreased in epithelial ovarian cancer and is related to the tumor histological subtype.

Publications

<i>NOTCH2</i> expression is decreased in epithelial ovarian cancer and is related to the tumor histological subtype.

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