MMP-9-1562 C/T single nucleotide polymorphism associates with increased MMP-9 level and activity during papillary thyroid carcinoma progression.

Papillary thyroid carcinoma (PTC), a common form of thyroid malignancy, displays significant variations in clinical features and outcome. The malignant transformation of the thyroid is driven by altered expression of many matrix-modulating enzymes, including matrix metalloproteinase-9 (MMP-9). A single nucleotide polymorphism in its promotor (-1562 C/T) is suspected to cause overexpression of MMP-9, which in turn contributes to development of a tumour unfavourable phenotype. The aim of this study was to investigate the impact of MMP-9 promotor genotype on MMP-9 expression in PTC samples, and to assess its value as a possible risk factor for developing PTC or its aggressive phenotype. A total of 105 PTC patients and 43 healthy controls were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. In order to estimate MMP-9 expression, PTC tissue sections were stained immunohistochemically. Statistical analysis showed that PTC cases and controls did not differ significantly in genotype frequencies (OR = 2.27, CI = 0.854-6.022). In PTC samples, the presence of the T allele was accompanied by elevated MMP-9 expression (p = 0.047) as well as a higher risk of developing extrathyroid extensions (p = 0.037) and high TNM stages (p = 0.009). Moreover, we observed overexpression of MMP-9 in cases presenting with extrathyroid invasion (p = 0.001), lymph node metastasis (p = 0.028), large tumour size (p = 0.031) and advanced stage (p = 0.005) compared to indolent tumours, along with enhanced enzymatic activity demonstrated by in situ zymography. Data suggests that MMP-9 (-1562 C/T) does not facilitate predisposition for PTC but affects the disease course by modulating MMP-9 expression. Genotyping MMP-9 provides important information which may prove beneficial in risk stratification of PTC patients.

Evaluation of survivin expression and its prognostic value in papillary thyroid carcinoma.

Overexpression of survivin, an inhibitor of apoptosis protein, has been found in a variety of human cancers, and is associated with tumor aggressiveness. In this study, we analyzed the expression of survivin in papillary thyroid carcinoma (PTC) and evaluated its clinical significance for predicting an aggressive course of disease at the time of diagnosis. Survivin expression was determined by immunohistochemistry in 104 tissue specimens of PTC, confirmed by Western blot and correlated with clinicopathological parameters. Of the tumors examined, 74 (71.15%) showed high cytoplasmic survivin expression. There was no association between high survivin expression and age, gender or tumor size. On the other hand, it was closely correlated with the presence of lymph node metastasis (P=0.009), and there was a tendency for correlation with extrathyroidal invasion (P=0.062). The high risk PTC group (TNM stage III-IV) was associated with high levels of survivin (P=0.027). These results indicate that survivin is an unfavorable molecule for PTC prognosis, and that its high expression may indicate a subset of PTC patients with a more aggressive disease course. Evaluation of its expression in fine needle aspiration samples could be a useful tool for the identification of those PTC patients who require more extensive surgery, careful follow-up and therapeutic strategy.