Mutations in DNA double strand breaks (DSB) repair genes are clearly associated with the pathogenesis of hereditary breast cancer. It is still unclear whether defects in this pathway may play a role in sporadic breast tumours development and progression. The aim of our study was to evaluate whether changes in expression of DSB repair genes is associated with breast cancer clinicopathological characteristics and patient’s outcome. Methods: We used a previously published breast cancer data set (van de Vijver et al. N Engl J Med 2009) that included clinical and gene expression data for 295 breast cancer cases. Data on local recurrence free survival, distant metasases free survival and overall survival were available for all patients. Reverse transcription quantitative PCR (qPCR) for mRNA determination and immunoistochemestry for protein analysis were used to confirm the association between the relevant genes analyzed and tumour clinicopathological characteristics on two independent data sets. Results: We correlated mRNA microarray expression data for 6 DSB repair genes (BRCA1, BRCA2, G22P1/ku70, ATR, RAD51, TP53) involved in key steps of the pathway with patient’s outcome using a Cox proportional regression model which also included the known breast cancer prognostic markers (ER, PR, Ki67 and HER2). Increased expression of the RAD51 gene was associated with a higher risk of local recurrence (HR 4.82, P=0.015) and development of distant metastases (HR 6.46, P=0.009). Together with other the other prognostic markers, RAD51 high expression was also a predictor of worse overall survival (HR 7.32, P=0.013). The analysis of an independent data set of 75 breast cancers by qPCR demonstrated that increased expression of the RAD51 gene was associated with a subgroup of Luminal A tumours characterized by absence of the progesterone receptor. This latter result was confirmed at protein expression levels by performing immunohistochemical analysis of the RAD51 protein on 58 breast cancer cases represented on a tissues microarray. Conclusions: Our results indicate that increased expression of the RAD51 gene may serve as an indicator of probability of tumour recurrence (local and distant) and overall survival in breast cancer patients.
RAD51 increased expression as a predictor of outcome in patients with breast cancer.
Fazio V. M.;
2011-01-01
Abstract
Mutations in DNA double strand breaks (DSB) repair genes are clearly associated with the pathogenesis of hereditary breast cancer. It is still unclear whether defects in this pathway may play a role in sporadic breast tumours development and progression. The aim of our study was to evaluate whether changes in expression of DSB repair genes is associated with breast cancer clinicopathological characteristics and patient’s outcome. Methods: We used a previously published breast cancer data set (van de Vijver et al. N Engl J Med 2009) that included clinical and gene expression data for 295 breast cancer cases. Data on local recurrence free survival, distant metasases free survival and overall survival were available for all patients. Reverse transcription quantitative PCR (qPCR) for mRNA determination and immunoistochemestry for protein analysis were used to confirm the association between the relevant genes analyzed and tumour clinicopathological characteristics on two independent data sets. Results: We correlated mRNA microarray expression data for 6 DSB repair genes (BRCA1, BRCA2, G22P1/ku70, ATR, RAD51, TP53) involved in key steps of the pathway with patient’s outcome using a Cox proportional regression model which also included the known breast cancer prognostic markers (ER, PR, Ki67 and HER2). Increased expression of the RAD51 gene was associated with a higher risk of local recurrence (HR 4.82, P=0.015) and development of distant metastases (HR 6.46, P=0.009). Together with other the other prognostic markers, RAD51 high expression was also a predictor of worse overall survival (HR 7.32, P=0.013). The analysis of an independent data set of 75 breast cancers by qPCR demonstrated that increased expression of the RAD51 gene was associated with a subgroup of Luminal A tumours characterized by absence of the progesterone receptor. This latter result was confirmed at protein expression levels by performing immunohistochemical analysis of the RAD51 protein on 58 breast cancer cases represented on a tissues microarray. Conclusions: Our results indicate that increased expression of the RAD51 gene may serve as an indicator of probability of tumour recurrence (local and distant) and overall survival in breast cancer patients.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.