Type IV collagen and CD44v6 expression in benign, malignant primary and metastatic ovarian tumors:: correlation with Ki-67 and p53 immunoreactivity

Objective. Loss of basement membrane (BM) components, such as type IV collagen has been demonstrated in ovarian cancer, but the associations with other molecules like CD44v6, involved in metastatic process of ovarian carcinoma, have not been fully analyzed. This study investigates the expression of type IV collagen, CD44v6 molecule in correlation with p53 and Ki-67 presence in primary and metastatic lesion of ovarian carcinoma to define their role in metastases of ovarian carcinoma. Methods. The expression of type TV collagen, CD44v6, p53, and Ki-67 was evaluated on frozen tissue sections from primary ovarian tumors (malignant n=37, benign n=16), metastatic lesions (n=29) and ascitic fluid cells (n=28). Protein expression of all studied biomarkers was evaluated in a subset of specimens using immunohistochemistry (IHC). Results. Type TV collagen expression in the primary ovarian carcinoma was positively correlated with International Federation of Gynecology and Obstetrics (FIGO) stage and tumor grade. Significant difference was observed for type IV collagen immunoreactivity in carcinoma cells in effusions when compared to corresponding primary tumors (P<0.001) and metastatic lesions (P<0.001). Likewise down-regulation of type IV collagen expression was seen in primary ovarian carcinomas (P=0.01), ascitic fluid cells (P<0.001), and metastases (P=0.003) when compared to benign ovarian neoplasms. CD44v6 expression was detected in a comparable percentage of primary carcinomas (51%) and metastatic lesions (52%). In cells isolated from ascitic fluid, CD44v6 immunopositivity was observed in 43% of cases. A comparative analysis of primary and metastatic tumors and carcinoma cells in effusion did not reveal differences in expression of CD44v6. Positivity of CD44v6 was found in 2116 (12%) of benign ovarian neoplasms. There were no significant differences between CD44v6 expression in benign neoplasms compared to primary malignant tumors and metastases (P>0.05). CD44v6 expression in primary ovarian carcinomas was associated with higher tumor grade (P=0.01) and histological type of tumors (P=0.01). An inverse relationship of type IV collagen expression with p53 and CD44v6 positivity in benign and malignant ovarian tumors was found (P>0.01). Type IV collagen expression was inversely correlated with p53 status (P=0.03) in metastatic lesions. A slight trend toward an inverse correlation between Ki-67 and type IV collagen expression was observed in both benign and malignant ovarian tumors and metastases. Conclusions. Our data suggest that observed inverse correlation of type IV collagen expression with p53, CD44v6, and slight with Ki-67 positivity in primary benign and malignant tumors indicates that these molecules may cooperate in the invasion and progression of ovarian carcinomas. (C) 2004 Elsevier Inc. All rights reserved.