High excision repair cross-complementation group 1 expression is associated with favorable prognostic factors in breast cancer

Abstract

Abstract. Distortion of DNA can inhibit transcription and replication, resulting in cell death. The nucleotide excision repair (NER) pathway recognizes and repairs DNA adducts. Excision repair cross-complementation group 1 (ERCC1) is a nuclease that serves a vital role in the NER pathway. Few studies have investigated ERCC1 expression in breast cancer. The aim of the present study was to analyze the association between clinicopathological features and ERCC1 expression in breast cancer. ERCC1 expression was studied in 224 invasive ductal carcinomas by immunohistochemical staining. ERCC1 expression was analyzed as an immunoreactive score, and classified into low and high expression groups. The association between immunohistochemical parameters and clinicopathological features was evaluated. High expression of ERCC1 was observed in 33 cases (14.7%) and was statistically associated with lower T stage (P=0.005), lower tumor size (P=0.001), no lymph node metastasis (P=0.044) and no lymphovascular invasion (LVI; P=0.004). Additionally, high ERCC1 expression was associated with a positive estrogen receptor (ER) (P=0.006) and progesterone receptor (PR) (P=0.001) expression status. Non-triple-negative breast carcinoma occurred more frequently in the high expression group (97%) than the low expression group; however, the difference was not statistically significant (P= 0.056). Overall and disease-free survival were also not significantly different between the two groups (P=0.989 and P=0.215, respectively). In conclusion, high ERCC1 expression is statistically associated with lower T stage, smaller tumor size, no lymph node metastasis, no LVI, and positive ER and PR expression. This suggests that ERCC1 is associated with favorable prognostic parameters in breast cancer. IntroductionBreast cancer is the most common malignancy in women worldwide. Various histological types of breast cancer have been reported, with invasive ductal carcinoma (invasive carcinoma of no special type) being the most frequently occurring type (1,2). Therefore, considerable effort has been devoted to identifying factors of prognostic and therapeutic significance in invasive ductal carcinoma. The immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR) and human epithelial growth factor receptor 2 (HER2) has been widely used for predicting the prognosis of breast cancer and for providing therapeutic strategies (3). Since Perou et al (4) reported the molecular features of breast cancer cells in 2000, the improvements in molecular techniques have provided a framework to establish molecular subtypes, namely luminal A, luminal B HER2 -, luminal B HER2 + , triple-negative, HER2 type, 5 negative phenotype and basal phenotype breast cancer (5,6). Breast cancer-expressed hormonal receptors, including ER and PR, or amplification of HER2, have been used in various targeted treatment approaches (7,8).A targeted therapy has not yet been established for TNBC. Therefore, chemotherapy with a platinum-based agent remains in use as a common...

Contribution of excision repair cross-complementing group 1 genotypes to triple negative breast cancer risk

“…A positive correlation was found between ERCC1 mRNA expression and DNA repair capacity in several studies [ 15 , 16 ]. The expression of ERCC1 was increased by cisplatin treatment in a time- and a dose-dependent manner in ovarian cancer cell lines [ 17 ]. However, the expression level of ERCC1 may have a dual function in breast carcinogenesis.…”

Extensive analysis of the molecular biomarkers excision repair cross complementing 1, ribonucleotide reductase M1, β-tubulin III, thymidylate synthetase, and topoisomerase IIα in breast cancer

“…Our findings about ERCC1 seemed not to be fully in accordance with the previous studies in breast cancer. Similarly, Kim et al [ 20 ] reported that high expression of ERCC1 was statistically associated with lower T stage, lower tumor size, no lymph node metastasis, positive ER and PR expression status, non-TNBC, and no lymphovascular invasion. By contrast, there was no association between ERCC1 expression and clinicopathological parameters, including age, histology, tumor stage at diagnosis, hormonal receptors (ER, PR) status, HER-2 status, presence of visceral disease, and pretreatment of metastatic disease, which has been studied by Metro et al [ 35 ] who analyzed ERCC1 expression using an automated and quantitative immunofluorescence technique.…”

“…High expression of ERCC1 is associated with favorable prognostic parameters such as a positive ER expression status in breast cancer. [ 20 ] In vitro experiment, RRM1 gene silencing can reverse paclitaxel resistance in human breast cancer cell line MCF-7/R. [ 21 ] Elevated TYMS expression was a detrimental factor for pemetrexed treatment in advanced breast cancer, indicating that it may be a biomarker to choose chemotherapy regimens.…”

Association of excision repair cross‐complimentary group 1 gene polymorphisms with breast and ovarian cancer susceptibility

“…15 Higher expression of ERCC1 was found to be associated with favorable prognostic factors for early stage breast cancer patients, but with poor outcome for those metastatic triple negative breast cancer patients treated with platinumbase chemotherapy. 16 This reminds us the complex regulation of ERCC1 in real world scenario of breast and ovarian cancer.…”