Reduced Annexin II Protein Expression in High-Grade Prostatic Intraepithelial Neoplasia and Prostate Cancer

Abstract

Annexin II is a calcium-dependent phospholipid-binding protein that plays a role in many cellular functions, including apoptosis, signal transduction, and cellular motility. The protein is strongly expressed in normal prostatic epithelial glands, but its expression in benign prostatic lesions has not been reported. Although commonly underexpressed in prostate cancer, the association of reduced expression with pathologic grade and stage is unknown. To compare annexin II expression in benign prostatic lesions with expression in high-grade prostatic intraepithelial neoplasia and prostate cancer, as well as to correlate expression levels with pathologic grade and stage. A semi-quantitative assessment of annexin II expression was performed in radical prostatectomy specimens from 74 patients and prostate needle core biopsy specimens from 13 patients. Foci with normal prostatic glands, atrophic glands, basal cell hyperplasia, high-grade prostatic intraepithelial neoplasia, and prostatic adenocarcinoma were evaluated. Annexin II expression was present in more than 50% of glands in most (>85%) samples of benign prostatic epithelium, atrophic glands, and basal cell hyperplasia. In high-grade prostatic intraepithelial neoplasia, annexin II staining was markedly reduced in epithelial cells but not in basal cells. Annexin II was absent or focally present in moderately differentiated adenocarcinoma but was retained in poorly differentiated adenocarcinomas. Reduced annexin II expression may be a useful diagnostic biomarker to help identify small foci of moderately differentiated adenocarcinoma on needle core biopsy specimens since it is consistently expressed in benign prostatic glands. Re-expression of annexin II in poorly differentiated adenocarcinoma may provide prognostic information.