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Level of Id-1 Protein Expression Correlates with Poor Differentiation, Enhanced Malignant Potential, and More Aggressive Clinical Behavior of Epithelial Ovarian Tumors

Institute of Clinical Pathology [M. S., S. F. S., C. L., R. H., P. B.], Institute of Neurology [T. S.], and the Department of Medical Computer Sciences, Section of Clinical Biometrics [H. H.], University of Vienna, A-1090 Vienna, Austria

Purpose: Id (inhibitor of differentiation/DNA binding) -1 is involved in neoangiogenesis, it antagonizes basic helix-loop-helix proteins, inhibits differentiation, and enhances cell proliferation. Aim of this study was to investigate Id-1 protein expression in epithelial ovarian tumors and its clinical relevance in ovarian cancer.

Experimental Design: We have investigated Id-1 expression by reverse transcription-PCR and Western blotting in ovarian cancer samples. On the basis of these results, Id-1 protein expression was determined by immunohistochemistry in 101 specimens of epithelial ovarian cancer, in 40 borderline tumors, and in 20 cystadenomas. In these cases, Id-1 expression was correlated with p21 expression, microvessel density, and survival.

Results: By immunohistochemistry, detectable expression of Id-1 was found significantly more often in ovarian cancers (74.3%) than in borderline tumors (32.5%) and cystadenomas (0%; P < 0.0001, ² test). Cancer samples with poor or moderate histological differentiation (G3/G2) showed significantly stronger Id-1 expression than cancer samples with high differentiation (G1; P = 0.021, Mann-Whitney test), and no association of Id-1 with p21 expression or microvessel density was found. In cancer samples strong or moderate expression of Id-1 was a strong predictor for shorter overall survival in uni- and multivariate analysis (P = 0.001, Cox-regression).

Conclusions: The level of Id-1 protein expression correlates with the malignant potential of ovarian tumors. In cancer samples, stronger Id-1 expression is associated with poor differentiation and more aggressive behavior of tumor cells, resulting in poor clinical outcome. Consequently, Id-1 inhibition in the future might be of benefit for patients with ovarian cancer.

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