Expression and prognostic significance of Fanconi anemia group D2 protein and breast cancer type 1 susceptibility protein in familial and sporadic breast cancer.

Abstract

Fanconi anemia group D2 protein (FANCD2) and breast cancer type 1 susceptibility protein (BRCA1), within the FA/BRCA pathway, are involved in the regulation of DNA damage repair, which is associated with breast cancer (BC) progression. The present study aimed to investigate BRCA1 and FANCD2 expression in breast cancer, and to highlight the association with patient clinical characteristics and prognoses. The BRCA1 and FANCD2 proteins were detected by immunohistochemistry in 335 tissue samples obtained from patients with BC, including 141 patients with familial BC (FBC), 147 patients with sporadic breast cancer (SBC) and 47 patients with benign breast tumors. Western blotting was used to detect the FANCD2 ubiquitination level in 56 frozen specimens that were randomly selected from the SBC group. Protein expression of BRCA1 in the FBC group was positively associated with tumor size, lymphatic invasion, Tumor-Node-Metastasis (TNM) stage, estrogen receptor (ER) status and FANCD2 expression. Protein expression of FANCD2 in the SBC group was positively associated with tumor size, TNM stage, ER status and Ki-67 index. Survival analyses revealed that BRCA1 expression was associated with the decreased disease-free survival (DFS) rate of patients with FBC (versus no BRCA1 expression) and that FANCD2 was associated with decreased DFS of patients with SBC (versus no FANCD expression). Univariable and multivariable analyses demonstrated that BRCA1 expression may be an independent prognostic factor in the FBC group. In the SBC group, FANCD2 high expression and low ubiquitination levels were considered as independent prognostic factors. In conclusion, the present study suggested that BRCA1 and FANCD2 expression, and FANCD2 ubiquitination levels, may be considered of novel potential prognostic value in patients with BC.