Significance of matrix metalloproteinase-1 and -3 gene polymorphisms and their expression in normal and neoplastic endometrium

Abstract

BackgroundMatrix metalloproteinases (MMPs) play a fundamental role in tissue degradation or remodeling and involved in all stages of tumor progression. However, the role of the MMPs polymorphisms with endometrial carcinoma has not been fully examined in Egyptian patients. Therefore, we planned this study to evaluate associations of the MMP-1 (−1607 1G/2G) and MMP-3 (−1171 5A/6A) polymorphisms and their immune reactive protein combinations with endometrial carcinoma susceptibility and prognosis in Egyptian patients. MethodsParaffin-embedded tissue samples from 40 women with endometrial carcinoma and 30 controls were immunohistochemically stained for MMP-1and MMP-3 expression. Tissue MMPs levels were analyzed by ELISA technique, and tissue samples were genotyped for MMP-1 and MMp-3 gene polymorphisms by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). Resultswe recorded a significant increase of MMP-1 levels in endometrial carcinoma patients more than controls, to be more increased with advanced stages and grades of the carcinoma. Whereas, the MMP-3 tissue levels showed non-significant changes among patients and controls and even among different stages and grades of cancer.Patients with endometrial carcinoma exhibited a higher distribution of MMP-11G/2G or 2G/2G genotypes compared with controls. Tumors containing the 2G allele expressed MMP-1 protein more frequently than those of 1G/1G genotype. The overall genotype and alleles distribution of the MMP-3 polymorphism in patients was not different from that of controls. The haplotype 2G-6A was associated with a significantly increased risk of endometrial carcinoma as compared with the 1G-5A haplotype. ConclusionThe MMP-1 (−1G/2G) SNP and MMP 2G/6A haplotype may modify susceptibility and are associated with a higher risk of endometrial carcinoma. Otherwise, the MMP-3 (5A/6A) promoter SNP is unlikely to be associated with endometrial carcinoma in the Egyptian population.