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

Up-regulated expression or loss of expression of various carbohydrate antigens on the surface of cancer cells has been associated with a metastatic phenotype and poor survival in epithelial malignancies of different origins. The object of this study was to investigate the expression of carbohydrate antigens in two groups of patients diagnosed with advanced-stage ovarian carcinoma-one with an extremely favorable outcome and the other with a uniformly poor survival. Sections from 76 paraffin-embedded blocks (primary ovarian carcinomas and metastatic lesions) from 45 patients diagnosed with advanced-stage ovarian carcinomas (FIGO stages III-IV) were immunohistochemically stained using five monoclonal antibodies for Lewis(y) (Le(y))(two antibodies), Sialyl Lewis(x) (Slex), Tn, and Sialyl Tn (STn) antigens. Patients were divided in two groups based on outcome. Long-term survivors (21 patients) and short-term survivors (24 patients) were defined using a double cut-off of 36 months for disease-free survival (DFS) and 60 months for overall survival (OS). Staining results for primary tumors and metastases were analyzed separately. Mean follow-up period was 70 months. The mean values for DFS and OS were 109 and 125 months for long-term survivors and 3 and 25 months for short-term survivors. Staining for all four antigens was seen in the majority of cases (range = 72-96%) and tended to be comparable in primary tumors and their metastases. However, absence of immunoreactivity for STn was seen in 9/38 (24%) metastatic lesions and only 1/38 (3%) primary tumors. This finding 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 front of some tumors, while Slex and Tn immunoreactivity did not relate to cell location. Primary tumors and metastatic lesions of long-term survivors displayed immunoreactivity patterns that were comparable to those of short-term survivors. In the evaluation of survival curves, more diffuse staining for 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). Le(y), Slex, STn, and Tn antigens are widely expressed in primary ovarian carcinomas and their metastases. Altered expression of Sialyl Tn is observed with tumor progression in a fraction of ovarian carcinomas. Expression of membrane carbohydrate residues is prevalent in tumors of both long-term and short-term survivors and does not appear to be a strong predictor of disease outcome. However, larger studies are needed to further elucidate the role of these molecules in ovarian carcinogenesis.

Davidson B ，Gotlieb WH ，Ben-Baruch G ，Kopolovic J ，Goldberg I ，Nesland JM ，Berner A ，Bjåmer A ，Bryne M ... -  《GYNECOLOGIC ONCOLOGY》

E-Cadherin complex protein expression and survival in ovarian carcinoma.

The aim of this study was to analyze the correlation between expression of E-cadherin complex proteins, epidermal growth factor receptor (EGFR), and c-erbB-2 and disease outcome in advanced-stage ovarian carcinomas. Sections from 75 primary ovarian carcinomas (=37) and metastatic lesions (=38) from 45 patients diagnosed with advanced-stage ovarian carcinoma (FIGO stage III-IV) were immunostained and evaluated for staining pattern, extent, and intensity. Patients were divided in two groups based on disease outcome. Long-term survivors (21 patients) and short-term survivors (24 patients) were defined using a double cutoff of 36 months for disease-free survival (DFS) and 60 months for overall survival (OS). Mean follow-up period was 70 months. The mean values for DFS and OS were 109 and 125 months for long-term survivors, as compared to 3 and 21 months for short-term survivors, respectively. Comparison of all primary and metastatic lesions showed upregulation of gamma-catenin protein expression in the latter (P = 0.05). When segregated according to disease outcome, the expression of all studied proteins, with the exception of EGFR, was more diffuse in tumors of short-term survivors. The presence of cytoplasmic staining for c-erbB-2 was associated with poor survival in the entire cohort (P = 0.007), as well as in primary tumors alone (P = 0.003), in survival analysis. Similar results were seen in the evaluation of primary tumors for gamma-catenin (P = 0.002). gamma-Catenin, and possibly c-erbB-2, are valid markers of poor survival in advanced-stage ovarian carcinoma.

Davidson B ，Gotlieb WH ，Ben-Baruch G ，Nesland JM ，Bryne M ，Goldberg I ，Kopolovic J ，Berner A ... -  《GYNECOLOGIC ONCOLOGY》

Carbohydrate antigen expression in primary tumors, metastatic lesions, and serous effusions from patients diagnosed with epithelial ovarian carcinoma: evidence of up-regulated Tn and Sialyl Tn antigen expression in effusions.

Davidson B ，Berner A ，Nesland JM ，Risberg B ，Kristensen GB ，Tropé CG ，Bryne M ... -  《HUMAN PATHOLOGY》

Caveolin-1 expression in advanced-stage ovarian carcinoma--a clinicopathologic study.

The aim of this study was to analyze the correlation among the expression of caveolin-1, the protein constituent of caveolae, and disease outcome in advanced-stage ovarian carcinomas. Sections from 76 primary ovarian carcinomas and metastatic lesions from 45 patients diagnosed with advanced-stage ovarian carcinoma (FIGO stages III-IV) were evaluated for caveolin-1 expression using immunohistochemistry. Patients were divided into long-term survivors and short-term survivors based on disease outcome. Twenty nonneoplastic fallopian tubes and ovaries were additionally studied. The mean follow-up period was 70 months. The mean values for disease-free survival and overall survival were 109 and 125 months for long-term survivors, compared to 3 and 21 months for short-term survivors, respectively. Caveolin-1 expression was localized to the cell membrane in 24/76 (32%) specimens and was detected in the cytoplasm in 52/76 (68%) cases. Both patterns were more often detected in metastases, when compared with primary tumors. In addition, membrane immunoreactivity was more often seen in tumor of short-term survivors. These differences did not reach statistical significance (P > 0.05). Combined membrane and cytoplasmic immunoreactivity was seen in 17/20 (85%) nonneoplastic lesions. Despite its role in tyrosine-kinase-mediated signal transduction in vitro studies, caveolin-1 expression in carcinomas showed no association with the protein expression of c-erbB-2 and epidermal growth factor receptor, evaluated in a previous study of this patient cohort. This study provides the first in vivo evidence of caveolin-1 membrane expression in human malignancies. Caveolin-1 is often expressed in advanced-stage ovarian carcinoma, but does not appear to be a powerful predictor of disease outcome in these tumors. The reduced expression level in carcinomas compared to nonneoplastic epithelium may point to a role for caveolin-1 as a tumor suppressor gene.

Davidson B ，Nesland JM ，Goldberg I ，Kopolovic J ，Gotlieb WH ，Bryne M ，Ben-Baruch G ，Berner A ，Reich R ... -  《GYNECOLOGIC ONCOLOGY》

Alphav integrin expression is a novel marker of poor prognosis in advanced-stage ovarian carcinoma.

Goldberg I ，Davidson B ，Reich R ，Gotlieb WH ，Ben-Baruch G ，Bryne M ，Berner A ，Nesland JM ，Kopolovic J ... -  《CLINICAL CANCER RESEARCH》