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CD44 Expression Indicates Favorable Prognosis in Epithelial Ovarian Cancer

Department of Pathology and Forensic Medicine, University of Kuopio and Kuopio University Hospital [S. S., M. A. A., K. V., V-M. K.], Department of Obstetrics and Gynecology, Kuopio University Hospital [M. A. A., S. V. S.], Department of Anatomy, University of Kuopio [R. H. T., M. I. T.], Kuopio, Finland, and Department of Pathology, Tampere University Hospital and University of Tampere [V-M. K.], Tampere, Finland

Purpose: The purpose of this study was to investigate the expression and prognostic significance of CD44 in epithelial ovarian cancer.

Experimental Design: We analyzed the expression of CD44 by immunohistochemistry in 307 epithelial ovarian cancers and evaluated its relation to hyaluronan, clinicopathological factors, and prognosis.

Results: Fifty-one percent of the tumors had a high proportion of CD44-positive cells (i.e., 10%), and this high CD44 expression was significantly associated with cancer cell-associated hyaluronan, well-differentiated tumor, mucinous histological type, and early stage of the tumor. High CD44 expression predicted better 5-year overall survival (50% versus 22%) and recurrence-free survival (70% versus 34%) in the univariate analyses (P < 0.00005 for both). In the Cox multivariate analyses, the independent predictors of overall survival at 5 years were primary residual tumor (P < 0.0005), International Federation of Gynecologists and Obstetricians (FIGO) stage (P = 0.001), histological grade (P = 0.014), adjuvant chemotherapy (P = 0.004), and stromal hyaluronan level (P < 0.0005), but not CD44. However, the expression of CD44 (P = 0.04) and stromal hyaluronan (P = 0.005) were both independent predictors of recurrence-free survival at 5 years, together with the size of the primary residual tumor (P < 0.0005) and histological type (P = 0.043).

Conclusions: The relatively frequent ectopic expression of CD44 on ovarian cancer cells is thus related to well-differentiated, early-stage tumor and long survival of the patients. Thus, whereas CD44-expressing cancer cells may adhere and implant to the hyaluronan-positive mesothelium, at least in model systems, high expression of CD44 in the tumor does not bring about an unfavorable prognosis.

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