Overexpression of H-Ryk in epithelial ovarian cancer: Prognostic significance of receptor expression

H-Ryk is an atypical receptor tyrosine kinase that is expressed in a differ entiation-specific manner in epithelial tissues. We have previously shown b y in situ hybridization and immunohistochemistry that H-Ryk is overexpresse d in malignant ovarian tumors. In addition, we have demonstrated that overe xpression of H-Ryk is transforming in vitro and irt vivo. To evaluate wheth er expression of H-Ryk is a prognostic factor in epithelial ovarian cancer, we carried out a retrospective study of 88 primary malignant ovarian tumor s (28 serous tumors, 11 mucinous tumors, 29 endometrioid tumors, 13 clear c ell tumors, 3 malignant mixed Mullerian tumors, I mixed epithelial tumor, 1 primary peritoneal tumor, 1 undifferentiated tumor, and 1 transitional car cinoma) diagnosed between 1990 and 1993 using immunohistochemistry. On univ ariate analysis, overall survival decreased significantly with age (P = 0.0 1); in patients with International Federation of Gynecology and Obstetrics (FIGO) stage II (P = 0.008), FIGO stage III (P < 0.001), and FIGO stage IV (P < 0.001) disease; and in patients with residual disease (residual diseas e less than or equal to 2 cm, P = 0.007; residual disease > 2 cm, P < 0.001 ) after surgery. In addition, overexpression of the H-Ryk receptor in malig nant epithelium (P = 0.04) and blood vessel (P = 0.01) was associated with a significantly decreased overall survival. H-Ryk blood vessel overexpressi on (P = 0.03), residual disease > 2 cm (P = 0.006), and residual disease le ss than or equal to 2 cm (P = 0.01) conferred a significantly shorter progr ession-free survival. No correlation was found between H-Ryk overexpression and age, histological subtype, degree of differentiation, FIGO stage, or r esidual disease. Overall, after adjustment for all of the prognostic factor s by multivariate analysis (Cox proportional hazards model), residual disea se was the most powerful prognostic indicator for overall survival (P < 0.0 01) and progression-free survival (P = 0.01) in this patient subset. This i mplies that H-Ryk acts cooperatively with other biological factors in the p athogenesis of ovarian cancer.