Immunohistochemical expression of topoisomerase II alpha and Her-2/neu in prostatic carcinoma and benign prostatic hyperplasia

Abstract

Background and purpose: Topoisomerase II a (Topo II a) and Her-2/neu are two important targeted therapeutic molecules. The immunohistochemical expression of both of them has not been widely studied in prostatic carcinoma and benign prostatic hyperplasia (BPH). The aim of this study was to evaluate the immunohistochemical expression of Topo II a and Her-2/neu in prostatic carcinoma and BPH and compare the expression patterns of both genes in cases of prostatic carcinoma in relation to Gleason score and hormonal status.

Material and methods: Paraffin blocks of 30 cases of prostatic carcinoma (categorized by Gleason score and hormonal status) and 5 cases of BPH presented to the Department of Pathology, Faculty of Medicine, Tanta University during the period from 2005 to 2008 were retrieved from the files. The immunohistochemical expression of Topo II a and Her-2/neu antibodies in the above-mentioned diagnostic categories was investigated and compared. The percentage of nuclei staining for Topo II a was semiquantitated; overexpression was defined as >or=5% nuclear staining. Her-2/neu immunoreactivity was scored from 0 to 3 + depending on membrane staining intensity and pattern.

Results: The expression of Topo II a varied significantly among the different studied groups (p<0.001). Topo II a expression increased significantly with increased Gleason score in prostatic carcinoma (p=0.001). Its expression in both moderately and poorly differentiated carcinomas was significantly higher than in BPH (p=0.005 and 0.002 respectively); however the difference between its expression in well-differentiated carcinoma and in BPH was statistically insignificant (p=0.171). Her-2/neu expression was higher in prostatic carcinoma than in BPH, however the difference did not reach the level of statistical significance (p=0.084). Also, the increase in its expression within prostatic carcinoma cases with increased Gleason score was statistically insignificant (p=0.100). There was a significant correlation between Topo II a and Her-2/neu expression (p=0.008, r=0.478). Hormone resistant carcinomas showed higher expression of Topo II a and Her- 2/neu than carcinomas with no hormone treatment, however, the differences were statistically insignificant (p=0.594 and 0.667 respectively).

Conclusions: Topo II a expression was significantly higher in poorly differentiated and moderately differentiated prostatic carcinoma compared to BPH. There was a significant increase in Topo II a expression with increased Gleason score. Her-2/neu expression was higher in prostatic carcinoma than in BPH, however the difference did not reach the level of statistical significance and the increase in its expression with increased Gleason score was also statistically insignificant. Topo II a and Her-2/neu were co-expressed significantly. Hormone resistant carcinomas showed higher expression of both markers, however, the differences were statistically insignificant. The latter finding may have important therapeutic implications, however, further large scale studies are required for confirmation.

Keywords: Topo II a - Her-2/neu - Prostatic carcinoma - BPH.