EMMPRIN (extracellular matrix metalloproteinase inducer) is a novel marker of poor outcome in serous ovarian carcinoma

EMMPRIN is a member of the immunoglobulin superfamily of adhesion molecules and has a role in the activation of several matrix metalloproteinases (MMP). The objective of this study was to investigate the expression of EMMPRIN in effusions, primary and metastatic tumors of serous ovarian carcinoma patients, as well as to evaluate its association with clinicopathologic parameters and with MMP and integrin expression. Eighty effusions and eighty-three solid lesions were evaluated for expression of EMMPRIN mRNA using in situ hybridization (ISH). Protein expression was studied in 75 effusions and 55 biopsies using immunohistochemistry (IHC). EMMPRIN mRNA and protein were detected in carcinoma cells in 63/80 (79%) and 64/75 (85%) effusions, respectively. Expression was similar in peritoneal and pleural effusions. EMMPRIN was co-expressed with MMP-1 (P < 0.001), MMP-9 (P = 0.006) and the αv (P = 0.013) and β1 (P = 0.029) integrin subunits. In solid lesions, EMMPRIN localized most often to tumor cells (51/83 using ISH 51/55 using IHC), but was also expressed in stromal and endothelial cells in approximately one third of the cases. EMMPRIN mRNA expression in tumor cells was most frequent in peritoneal metastases (P = 0.03). EMMPRIN expression in carcinoma cells of solid tumors showed an association with that of MMP-9 (P = 0.018), while labeling of stromal cells showed co-localization with the β1 integrin subunit (P = 0.043). In survival analysis, EMMPRIN protein expression in stromal cells of primary tumors (P = 0.012) and in endothelial cells of all solid tumors (P = 0.023) correlated with poor survival. In conclusion, EMMPRIN is a novel prognostic marker in ovarian carcinoma, and is co-expressed with other metastasis-associated molecules in this malignancy. The identical phenotype of carcinoma cells in pleural and peritoneal effusions provides further evidence to our theory that cells at these sites share similar genotypic and phenotypic profiles.