Immunohistochemical staining for DNA topoisomerase II-alpha in benign, premalignant, and malignant lesions of the prostate

BACKGROUND. The DNA topoisomerase II-alpha (topo II-alpha)-targeting drug e toposide was recently shown to be an active agent in the combined chemother apy of hormone-insensitive prostatic carcinoma. Aside from being the molecu lar target of etoposide, topo II-alpha is also a cell proliferation marker. Much experimental data indicate that cells sensitive to topo II-targeting chemotherapeutic drugs are rapidly proliferating and show elevated topo LI expression. There is little information concerning toro II expression in le sions of the prostate. METHODS. Paraffin blocks from cases of invasive prostatic carcinoma, prosta tic intraepithelial neoplasia, and prostatic nodular hyperplasia were retri eved from the surgical pathology files at the University of Utah Health Sci ences Center. Using a new immunohistochemical stain, specific for the alpha isoform of DNA topo II, enzyme expression was evaluated in 54 prostatic ad enocarcinomas, 22 lesions of high-grade prostatic intraepithelial neoplasia (PIN), and 10 cases of benign prostatic nodular hyperplasia. Results were semiquantitated by determining for each case a topo II-alpha index, which r epresented the percent of positively staining cells. RESULTS. The average topo II-alpha index for well-differentiated prostatic adenocarcinomas (Gleason scores 2-4) was 1.5 +/- 0.9; for moderately differ entiated tumors (Gleason scores 5-7), 3.1 +/- 2.4; and for poorly different iated tumors (Gleason scores 8-10), 6.7 +/- 5.5. The average topo II-alpha index for all invasive prostatic adenocarcinomas was 4.0 (range, 0-19.0). B enign prostatic nodular hyperplasia had the lowest average topo II-alpha in dex, of 0.54 (range, 0.2-1.0). The average topo II-alpha index of 2.3 (rang e, 0-8.6) for high-grade prostatic intraepithelial neoplasia was intermedia te between the invasive tumors and benign prostate. CONCLUSIONS. Topo II-alpha expression in carcinoma of the prostate correlat es with Gleason score. The carcinomas with the highest expression of enzyme are more poorly differentiated and have the highest Gleason scores. Prosta tic nodular hyperplasia shows little expression of topo II-alpha. Prostatic intraepithelial neoplasia has an average toro II-alpha index intermediate between nodular hyperplasia and carcinoma. Prostate 42:280-286, 2000. (C) 2 000 Wiley-Liss, Inc.