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Versican, a proteoglycan previously reported to increase in other malignant tumours, was studied immunohistochemically in 299 primary epithelial ovarian cancers, their 43 metastases and 6 normal ovaries to evaluate its prognostic value and relation to hyaluronan, another extracellular matrix molecule increased in cancer and a binding partner of versican. The stainings were scored according to the area percentage of strong versican signal of total peri- and intratumoural stroma as low (<15%) or high (>or=15%). Epithelial staining of the tumours was scored as positive or negative. Low and high area percentage of strong stromal versican staining were observed in 133 and 166 carcinomas, respectively. A low area percentage of strong stromal versican staining correlated with mucinous histology (p = 0.019) and early International Federation of Gynecologists and Obstetritians (FIGO) stage (p < 0.0005), whereas a high percentage was associated with reduced 5-year survival rate of the patients (44% vs. 32%; p = 0.032). Versican was associated with the cancer cells in 151 tumours and correlated with clear cell histology (p < 0.0005), early FIGO stage (p = 0.049) and increased recurrence-free survival (63% vs. 47%; p = 0.032). However, in Cox's multivariate analyses with the conventional prognostic factors included, neither stromal nor cancer cell-associated versican reached a significant prognostic value. Versican is thus enriched in the malignant stroma surrounding and promoting the growth of ovarian cancer, probably acting with hyaluronan, and associates with unfavourable prognosis but does not constitute an independent indicator of patient survival., (Copyright 2003 Wiley-Liss, Inc.)

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., >/==" BORDER="0">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.