Overexpression of RAD51 occurs in aggressive prostatic cancer

Abstract

Aims: To test the hypothesis that, in a matched series of prostatic cancers, either with or without BRCA1 or BRCA2 mutations, RAD51 protein expression is enhanced in association with BRCA mutation genotypes.

Methods and results: RAD51 expression identified immunohistochemically was compared between prostatic cancers occurring in BRCA1 or BRCA2 mutation carriers and controls. RAD51 protein expression in the cytoplasm and nuclei of the benign tissues was significantly less than in the malignant tissues (P < 0.001). In all cancers, cytoplasmic expression of RAD51 was more prevalent and associated with higher Gleason score (P < 0.05) irrespective of BRCA mutational status, than its expression in benign tissues (P < 0.001). Although nuclear immunoreactivity was not observed in BRCA-associated cancers with Gleason score < or =7, it was significantly increased in all other groups of prostatic cancers when compared with benign tissues (P < 0.001).

Conclusions: RAD51 protein is strongly expressed in high-grade prostatic cancers, whether sporadic or associated with BRCA germ-line mutations. Distinct localization of RAD51 between cytoplasm and nucleus, particularly in cancers of Gleason score < or =7, reflects distinct levels of RAD51 regulatory activity, from transcription to DNA repair. This biomarker may be of value in identifying patients requiring urgent treatment at diagnosis as well as in analysing biological mechanisms underlying aggressive phenotype of human prostatic cancer.

Figure 1

[A] BRCA2: In-situ and invasive prostatic carcinoma in which the in-situ components express high levels of nuclear RAD51 staining (++). [B] BRCA1: Invasive prostatic carcinoma expressing high levels of nuclear RAD51 in the nuclei of invasive carcinoma cells. The in situ component is predominantly unstained or the cells are expressing RAD51 within the cytoplasm (+). [C] BRCA2: Nests of poorly-differentiated prostatic carcinoma (Gleason 4+4) carcinoma expressing nuclear RAD51 (+++) in approximately 40% of nuclei. [D] BRCA2: Poorly-differentiated (Gleason 5+5) invasive prostatic adenocarcinoma expressing RAD51 (++) within the nuclei of approximately 40% of nuclei in this field. Low levels of cytoplasmic staining are also identified. [E] BRCA2: Nests and cords of poorly-differentiated (Gleason 5+5) prostatic carcinoma expressing high levels of RAD51 (+++) in the cytoplasm of the invasive carcinoma cells. No nuclear staining is identified. [F] BRCA1: Cribriforming prostatic adenocarcinoma (Gleason 4+4) expressing moderate levels of RAD51 (++) within the cytoplasm of the malignant cells. No nuclear staining is evident.