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v Integrin Expression Is a Novel Marker of Poor Prognosis in Advanced-stage Ovarian Carcinoma

Department of Pathology [I. G., J. K.] and Division of Gynecologic Oncology [W. H. G., G. B-B.], Sheba Medical Center, Tel-Hashomer 52621, Israel; Department of Pathology, The Norwegian Radium Hospital [B. D., A. B., J. M. N.] and Department of Oral Biology [M. B.], University of Oslo, Norway, Montebello N-0310 Oslo, Norway; and Department of Pharmacology, Faculty of Medicine, Hebrew University, Jerusalem 91120, Israel [R. R.]

Purpose: To analyze the possible correlation between expression of the v and ß1 integrin chains and survival in advanced-stage ovarian carcinomas, studying two patient groups with extremely different disease outcome.

Experimental design: Sections from 56 primary ovarian carcinomas and metastatic lesions from 34 patients diagnosed with advanced-stage ovarian carcinoma (Fédération Internationale des Gynaecologistes et Obstetristes stages III-IV), divided into long-term (16) and short-term (18) survivors, were evaluated for expression of v and ß1 integrin chains using mRNA in situ hybridization. Protein expression was additionally studied in 52 specimens using immunohistochemistry.

Results: The mean values for disease-free survival and overall survival were 115 and 132 months for long-term survivors, as compared with 4 and 23 months for short-term survivors, respectively. Expression of v integrin mRNA was observed in carcinoma (18 of 56; 32%) and stromal (17 of 56; 30%) cells. ß1 integrin mRNA was similarly detected in carcinoma (25 of 56; 47%) and stromal (19 of 56; 34%) cells. No significant differences were observed when primary and metastatic lesions were compared (P > 0.05). v integrin mRNA was present more often in carcinoma cells in tumors of short-term survivors (P = 0.017 for carcinoma cells). In univariate survival analysis for all cases, v integrin mRNA expression in tumor cells correlated with poor survival (P = 0.012). This finding retained its predictive power in a multivariate survival analysis, in which all of the molecules studied previously in this patient cohort were included (P = 0.031). Immunohistochemistry confirmed the differences in v integrin expression in tumor cells of short-term as compared with long-term survivors, whereas ß1 integrin protein expression was comparable in the two groups.

Conclusions: To our best knowledge, this is the first evidence associating integrin expression with poor survival in ovarian carcinoma. v integrin is, thus, a novel prognostic marker in advanced-stage ovarian carcinoma.

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