Rad51 expression is associated with estrogen and progesteron receptor status in sporadic breast cancer

The maintaining of genome stability is one of the main mechanisms involved in prevention of tumor formation thus a number of intricate networks have evolved in eukaryotic cells to respond to exogenous and endogenous genotoxic stimuli. In an initial study we have analyzed mRNA expression changes of 15 genes involved in both Homologous Recombination (HR) and Non Homologous End Joining (NHEJ) pathways on paired normal and cancer tissues from 20 patients. Three genes, ATR, RAD51 and G22P1/Ku70 were differentially expressed in tumours as compared with normal tissues. To confirm data from the training set we analyzed by real-time quantitative PCR paired normal tissues and tumour specimens obtained from 55 breast cancer patients. Since high variability was found in normal tissues for each case we calculated the relative expression ratio (RER) in tumour samples as compared with normal tissue. When relative expression ratios were correlate with tumours clinical characteristics, only RAD51 showed higher RERs in the group of tumours with ER-positive/PR-negative phenotype as compared with the ER-positive/PR-positive and ER-positive/PR-negative subgroups (Kruskall-Wallis p=0.07). We used commercially available antisera to evaluate protein expression of RAD51 on a panel of 59 primary breast cancer and 3 fibroadenoma samples represented on a tissue microarray (BR641 Biomax.). RAD51 immunostaining was detected in 39 of the 58 (67%) breast cancers represented on a tissue microrray (median value 30%, range 0-70%). No staining was detected in the three fibroadenomas represented on the tissue microarray and in normal breast tissues represented in the tumor. When IHC results were compared with tumour clinicopathological characteristics, the percentage of RAD51 stained cells was higher in PR negative patients as compared with positive cases (P=0.002 Mann Whitney test) and this inverse correlation was confirmed in logistic regression analysis (P=0.0035). Interstingly all tumours ER-positive/PR-negative phenotype (12 out of 12) showed RAD51 immunostaining. Moreover, in this subgroup statistically significant higher levels of RAD51 protein were also detected as compared with ER-positive/PR-positive and ER-negative/PR-positive patients subgroups (Kruskall-Wallis p=0.004). In particular the analysis between groups demonstrated statistically significant differences between the ER-positive/PR-positive group and the ER-positive/PR-negative groups (Dunn Test P<0.01). Our data suggest an involvement of the RAD51 gene in the pathogenesis and progression of breast cancer and indicate that RAD51 overexpression may represent a specific feature of a subgroup of the Luminal subtype.