Comparative quantitative immunohistochemical and immunoradiometric determinations of cathepsin D in endometrial adenocarcinoma: predictors of tumor aggressiveness.

Abstract

Previous comparisons of results of biochemical and immunohistochemical assays for Cathepsin D protease (CD) have conflicted in breast tumors and have not been applied to endometrial adenocarcinomas. We studied CD levels in 31 endometrial adenocarcinomas comparing immunoradiometric assay (IRA) of tumor cytosol with quantitative immunohistochemistry (QIH). Corresponding formalin-fixed paraffin-embedded sections were stained with a polyclonal antibody and measured with the CAS 200 Image Analyzer using a modified cytoplasmic antigen quantification program. Significant and trended increases in CD levels by IRA and QIH were similarly seen in high-grade tumors (IRA p < 0.001; QIH p < ns), papillary serous carcinoma subtype, and cases with deep myometrial invasion (IRA p < 0.005; QIH p < 0.04). Higher mean CD levels by QIH correlated significantly with positive lymph node status (LN+ 0.18 U/cell; LN- 0.09 U/cell; p < 0.03). No correlation of CD by IRA or QIH with estrogen- and progesterone-receptor tumor status was seen. We conclude that image quantification immunohistochemistry is an objective and sensitive method for determining tumor CD levels, CD by QIH directly correlates with standard prognostic indicators such as myometrial invasion and lymph node metastasis, and CD by QIH may prove clinically useful as a predictive adjuvant study for endometrial adenocarcinoma biopsy specimens.