Matrix metalloproteinase 7 (MMP-7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) downregulation complements PALG1 oncogene overexpression in pleomorphic adenoma pathogenesis

Abstract

Pleomorphic adenoma (PA) is the most common neoplasm of salivary glands and consists of epithelial and mesenchymal components. Although a benign lesion, it harbors a potential for recurrence and malignant transformation. Also, due to its histological diversity and unpredictive behavior PA can represent both diagnostic and therapeutic challenge. Matrix metalloproteinases (MMPs) are well known modifiers of extracellular matrix (ECM) PA component and in conjunction with their endogenous tissue inhibitors (TIMPs) may influence PA tumor biology. PLAG1 oncogene also has an important role in PA; however, neither the exact mechanisms of its influence nor its interactions with other genes are completely elucidated. The aims of this study were to assess the expression of PLAG1, MMP-2, MMP-7, MMP-9, TIMP-1 and TIMP-2 genes in PAs, and find a possible association of gene expression levels with clinical/epidemiological parameters of PA patients. Relative mRNA levels were assessed using Quantitative real-time PCR analyses in 15 PAs of the parotid gland and 5 normal salivary glands (NSGs). A statistically significant overexpression of PLAG1 was observed in PA compared to NSG samples (P=0.010); PA had 5.48 times higher mRNA levels than NSG. Out of the three analyzed MMP genes, significantly lower levels of MMP-7 were found in PA patients (P=0.026). TIMP2 was also downregulated in PA samples, compared to NSGs (P=0.040). MMP-7 and TIMP-2 mRNA levels were decreased 2.95 and 2.85 times respectively, in PA samples. No association was found between gene expression and clinical/epidemiological PA parameters. Our results suggest that PLAG1 overexpression with concomitant MMP7 and TIMP2 downregulation may contribute to PA development.