Distribution of HER-2 overexpression in ovarian carcinoma tissue and its prognostic value in patients with ovarian carcinoma: from the Danish MALOVA Ovarian Cancer Study

Abstract

Background: The HER-2 (Human Epidermal Growth factor receptor-2, also known as c-erb-2/neu) protooncogene encodes a transmembrane receptor protein, M(r) 185,000. Studies have shown that the HER-2 oncogene is overexpressed in approximately 25-30% of ovarian carcinoma (OC) cases, but to the authors' knowledge, to date no consensus regarding overexpression and prognosis has been possible. The objective of the current study was first to analyze the presence of HER-2 overexpression in tissue from Danish OC patients and correlate the distribution of HER-2 overexpression with clinical and biochemical data and second to investigate the value of HER-2 overexpression as a prognostic marker in OC and to compare this value with the prognostic value of other biochemical markers.

Methods: The study population was comprised of the first 181 patients diagnosed with epithelial OC who were included in the MALOVA study. The staining procedure for HER-2 overexpression was performed using the p185 antibody.

Results: HER-2 overexpression was found in 95 of the 181 investigated cases (52.5%), in which 71 carcinomas (39.2%) were weakly positive (1+) and 24 carcinomas (13.3%) were moderately (2+) to intensely positive (3+). Increased HER-2 expression was found to be correlated with reduced survival. Significant differences in survival between patients with (1+, 2+, and 3+) and those without HER-2 overexpression were found for patients with International Federation of Gynecology and Obstetrics (FIGO) Stage I, Stage III, and Stage III/IV OC (Stage I: P = 0.021; Stage III: P = 0.0078; and Stage III/IV: P = 0.0054). Multivariate survival analyses including all 181 OC patients demonstrated that HER-2 overexpression is a prognostic marker (P = 0.003) together with disease stage, serum tetranectin level, and patient age. For patients with Stage III OC, the only independent prognostic factors detected were HER-2 overexpression (P = 0.009) and serum tetranectin level (P <or= 0.0001).

Conclusions: The results of the current study show that HER-2 overexpression has prognostic value both in univariate and multivariate survival analyses. Therefore, the clinical relevance of this observation should be established conclusively by therapy that targets HER-2 in a prospective Phase II clinical trial.