Endocrine Abstracts

Background: Matrix metalloproteinase-9 (MMP-9) is an important mediator of invasion and metastasis in neoplasia. The single nucleotide 1562 C/T polymorphism in the promoter region of the MMP-9 genewas shown to increase gene expression and was studied as a susceptibility factor for various cancers.

Aim: We aimed to evaluate the impact of the MMP-9 promoter genotype on the risk of developing papillary thyroid cancer (PTC) and to correlate cancer patient genotype with the pre-surgery serum MMP-9 levels and clinical and pathological features of tumor aggressiveness.

Patients and Methods: We evaluated 213 patients referred for thyroidectomy, divided according to pathology into: benign disease (BD) (n = 102) and PTC (n = 111). Genomic DNA was isolated from whole blood in all patients and the presence of theMMP-9 1562 C/T polymorphism was evaluated by PCR-RFLP analysis. Pre-surgical serum MMP-9 levels were available in 90 BD and 81 PTC patients. MMP-9 was measured by Elisa (R&D Systems).

Results: Genotype frequencies were in Hardy-Weinberg equilibrium for both patients and controls. T allele was significantly more frequent in PTC patients compared to BD: the combined CT + TT genotype was present in 37 PTC (33.3%) compared to 16 BD patients (15.7%), χ² = 8.86, CI [1.384–5.219], P = 0.0029. The 1562 C/T genotype did not significantly correlate with presurgical serum MMP-9 levels in either BD or PTC patients; in cancer patients the genotype was not associated with histological subtype, presence of invasion or risk of recurrence. However, the CT + TT genotype was significantly more frequent in tumors smaller than 1 cm compared to larger tumors (P = 0.016) and after excluding small intra-thyroidal micropapilllary carcinomas (MPTC) (N = 21), the association between genotype and BD/PTC diagnosis was lost (P = 0.09).

Conclusion: The presence of the functional 1562 C/T polymorphism in the promoter region of the MMP-9 gene may indicate susceptibility to develop thyroid cancer. However, the association between the T allele and intrathyroidal clinically non-relevant MPTC may suggest that although this may be a predisposing factor, other genetic/epigenetic events are needed for cancer progression. The 1562 C/T polymorphism might not be clinically useful as a prognostic factor.

The study was funded by UEFISCDI grant PN-II-PT-PCCA-2011-3.2 no.135/2012.