Epithelial membrane protein‐2 expression is an early predictor of endometrial cancer development

Abstract

BACKGROUND: Endometrial cancer (EC) is a common malignancy worldwide. It is often preceded by endometrial hyperplasia, whose management and risk of neoplastic progression vary. Previously, the authors have shown that the tetraspan protein epithelial membrane protein-2 (EMP2) is a prognostic indicator for EC aggressiveness and survival. Here the authors validate the expression of EMP2 in EC, and further examine whether EMP2 expression within preneoplastic lesions is an early prognostic biomarker for EC development. METHODS: A tissue microarray (TMA) was constructed with a wide representation of benign and malignant endometrial samples. The TMA contains a metachronous cohort of cases from individuals who either developed or did not develop EC. Intensity and frequency of EMP2 expression were assessed using immunohistochemistry. RESULTS: There was a stepwise, statistically significant increase in the average EMP2 expression from benign to hyperplasia to atypia to EC. Furthermore, detailed analysis of EMP2 expression in potentially premalignant cases demonstrated that EMP2 positivity was a strong predictor for EC development. CONCLUSIONS: EMP2 is an early predictor of EC development in preneoplastic lesions. In addition, combined with our previous findings, these results validate EMP2 as a novel biomarker for EC development. Cancer 2010;116:4718-26.

Rationale and Preclinical Efficacy of a Novel Anti-EMP2 Antibody for the Treatment of Invasive Breast Cancer

“…Preparation of breast cancer cell lines or tissue lysates for western blotting has been described previously (27). Cells were lysed in Laemmli buffer, and for EMP2 detection, were treated with N-glycosidase F (New England Biolabs, Beverly, MA) to remove N-link glycosylation (15).…”

“…Belonging to the growth arrest specific-3 (GAS3) family of tetraspan proteins, elevated EMP2 levels have been observed in advanced ovarian and endometrial tumors (7, 8), and its expression inversely correlated with endometrial cancer patient survival (9). This effect could be recapitulated through xenograft modeling as endometrial tumors where EMP2 expression was increased showed enhanced tumor growth (10).…”

Loss of epithelial membrane protein-2 expression confers an independent prognosticator in nasopharyngeal carcinoma: a cohort study

“…Due to non-neoplastic peritoneal, surface tissues were complete negative for EMP2 staining, thus EMP2 was regarded as increased expression in tumour cells in ovarian cancer 20. Moderately intense diffuse immunohistochemical stainings of tumour cell cytoplasm were identified in endometrioid adenocarcinoma, serous carcinoma, mixed endometrioid and serous carcinoma, mixed endometrioid and clear cell carcinoma 21. On the other hand, compared with undifferentiated ones, predominant expressions of EMP2 in cytoplasm and/or membrane of squamous metaplasias and non-keratinising NPCs were found in our study, suggesting that loss of EMP2 expression might change its interactions with some membrane proteins in NPC.…”

Expression of thyroid transcription factor-1 in normal endometrium is associated with risk of endometrial cancer development

“…[18] Briefly, 535 formalin-fixed, paraffin-embedded archival endometrial tissue samples were randomly collected from 207 patients by curettage, biopsy, or hysterectomy procedures dating from 1982 to 2002 (Department of Pathology and Laboratory Medicine, UCLA Medical Center) with institutional review board approval. Of the 207 patients, 150 had at least two specimens collected during separate procedures, for a total of 457 ‘serial’ specimens.…”

“…Nuclear positivity for each case was expressed as a percentage and was calculated from the mean pooled value of TTF-1 expression from which there were multiple informative spots as previously described. [18] A positive case was defined as any nuclear TTF-1 expression in endometrial glandular cells present. For all results, p<0.05 was considered significant.…”