BRCA1 Single Nucleotide Polymorphisms And Microsatellite Instability In Endometrial Cancer And Their Association With Patient Prognosis In The Chinese Population

Objective:This study aimed to investigate the presence of BRCA1 single nucleotide polymorphisms (SNPs) and microsatellite instability (MSI) in Chinese patients with endometrial cancer (EC) and to evaluate factors affecting prognosis.Methods:Endometrial tissue was obtained from 97 cases:49 cases of EC, 20 cases with endometrial atypical hyperplasia and 28 cases with normal endometrium. Polymerase chain reaction-single-strand conformation polymorphism was performed to detect MSI in D17S579 and D17S1349, and to detect SNPs in five BRCA1 exons. Clinicopathologic features and overall survival were compared between patients with and without SNPs and MSI, and a multivariate analysis was performed to identify prognostic factors.Results:There were significant differences in the presence of single nucleotide polymorphisms among the endometrial cancer, endometrial atypical hyperplasia and normal endometrium groups (x2=6.450, P=0.040). Spearman correlation analysis showed that the BRCA1 SNP-positive rate and BRCA1 protein expression were negatively correlated (r=-0.482, P=0.000). The BRCA1 SNP-positive rate was associated with muscular infiltration depth (r=-0.482, P=0.000), no relationship was found with pathology grade, clinical stage, lymph node metastasis, and histopathology (P> 0.05). In the total samples of D17S579 and D17S1349, three groups were significantly different:34.69%(17/49) in endometrial cancer group,10%(2/20) in endometrial atypical hyperplasia group and 7.14%(2/28) in normal endometrium group (x2=11.208, P=0.004). BRCA1 MSI positive rate was related to the pathology grade and clinical stage, but no relationship was found with muscular infiltration depth, lymph node metastasis and histopathology types. MSI positive rate was higher in G3 group than that in Gl or G2 group. MSI positive rate was higher in clinical Ⅲ～Ⅳ stage than that in clinical Ⅰ～Ⅱ stage. In endometrial cancer group, BRCA1 MSI positive rate and BRCA1 protein expression were in moderate correlated negatively (r=-0.779, P=0.000). Median overall survival was significantly lower in patients with BRCA1 MSI or SNPs. The multivariate analysis showed that pathology grade (P= 0.014) and SNP-positivity (P= 0.011) were independent risk factors affecting the prognosis of EC patients.Conclusion:BRCA1 single nucleotide polymorphisms or microsatellite instability was associated with the occurrence and development of endometrial cancer.