Expression of carbohydrate antigens in advanced-stage ovarian carcinomas and their metastases - A clinicopathologic study

Objective. Up-regulated expression or loss of expression of various carbohy drate antigens on the surface of cancer cells has been associated with a me tastatic phenotype and poor survival in epithelial malignancies of differen t origins. The object of this study was to investigate the expression of ca rbohydrate antigens in two groups of patients diagnosed with advanced-stage ovarian carcinoma-one with an extremely favorable outcome and the other wi th a uniformly poor survival. Methods. Sections from 76 paraffin-embedded blocks (primary ovarian carcino mas and metastatic lesions) from 45 patients diagnosed with advanced-stage ovarian carcinomas (FIGO stages III-TV) were immunohistochemically stained using five monoclonal antibodies for Lewis(y) (Le(y))(two antibodies), Sial yl Lewis(x) (Slex), Tn, and Sialyl Tn (STn) antigens. Patients were divided in two groups based on outcome. Long-term survivors (21 patients) and shor t-term survivors (24 patients) were defined using a double cut-off of 36 mo nths for disease-free survival (DFS) and 60 months for overall survival (OS ). Staining results for primary tumors and metastases were analyzed separat ely. Results. Mean follow-up period was 70 months. The mean values for DFS and O S were 109 and 125 months for long-term survivors and 3 and 25 months for s hort-term survivors. Staining for all four antigens was seen in the majorit y of cases (range = 72-96%) and tended to be comparable in primary tumors a nd their metastases. However, absence of immunoreactivity for STn was seen in 9/38 (24%) metastatic lesions and only 1/38 (3%) primary tumors. This fi nding did not reach statistical significance (P > 0.05). A combined pattern of membranous and cytoplasmic staining was predominant in the majority of cases. Enhanced staining for Le(y) and STn was detected in the invasive fro nt of some tumors, while Slex and Tn immunoreactivity did not relate to cel l location. Primary tumors and metastatic lesions of long-term survivors di splayed immunoreactivity patterns that were comparable to those of short-te rm survivors. In the evaluation of survival curves, more diffuse staining f or Slex showed marginal correlation with poor survival (P = 0.05), while a trend toward poorer survival was seen in tumors that were more extensively stained for Le(y) and Tn (P > 0.05). Conclusions. Le(y), Slex, STn, and Tn antigens are widely expressed in prim ary ovarian carcinomas and their metastases, Altered expression of Sialyl T n is observed with tumor progression in a fraction of ovarian carcinomas. E xpression of membrane carbohydrate residues is prevalent in tumors of both long-term and short-term survivors and does not appear to be a strong predi ctor of disease outcome. However, larger studies are needed to further eluc idate the role of these molecules in ovarian carcinogenesis, (C) 2000 Acade mic Press.