Expression of epithelial membrane protein-2 is associated with endometrial adenocarcinoma of unfavorable outcome

BACKGROUND: Epithelial membrane protein 2 (EMP2) is an estrus-regulated tetraspan protein that is required for endometrial competence in blastocyst implantation. EMP2 controls surface levels of several classes of integrin and other cell-interaction molecules, and their trafficking to glycolipid-enriched lipid raft domains is important in receptor signaling. These features suggest that EMP2 may contribute to neoplastic traits of endometrial cancer. The objective of this study was to determine the prevalence of EMP2 expression in endometrial neoplasms and its clinical significance. METHODS: EMP2 immunophenotype, histologic diagnosis, grade, the presence of lymphovascular invasion, disease stage, and clinical follow-up were determined for 99 endometrial cancers. RESULTS: Significant EMP2 expression (EMP2 positive) was observed in 12 of 99 cancers (9 endometrioid [6 International Federation of Gynecology and Obstetrics Grade 3], 1 serous, 1 mixed endometrioid and serous, and 1 mixed endometrioid and clear cell), and weak EMP2 expression was observed in 11 cancers. EMP2-positive tumors were more likely than others to be myometrium invasive, high stage, and recurrent, persistent, or fatal. The overall median survival for patients with EMP2-positive tumor was only 23 months, whereas the medial survival was not reached for patients with EMP2-weak and EMP2-negative tumors. The median disease-free interval was only 11 months for patients with EMP2-positive tumors and was not reached for patients with EMP2-weak and EMP2-negative tumors. A multivariate analysis of disease-free survival demonstrated independent, negative prognostic significance for EMP2 expression, high stage, and high-risk histologic subtypes. CONCLUSIONS: EMP2 expression is a feature of some prognostically unfavorable endometrial cancers. Its utility for clinical decision making and its biologic role in endometrial cancer deserves further study in a larger series of patients.