Clinical Significance of MMP-2, MMP-9 and HIF-1alpha Expression in Thyroid Micropapillary Cancer

ABSTRACT

PURPOSE: Papillary Thyroid Microcarcinoma (PTMC) is rapidly increasing due to increased interests in the public health care system and improvements in ultrasonographic instruments and fine-needle-aspiration technique. The aim of this study is to investigate relationships between clinicopathologic features and molecular markers of PTMC and to help in developing therapeutic strategies in PTMC. METHODS: Tissue samples from patients with 38 PTMC and 21 benign thyroid tumors that were operated on from Jan. 2006 to Nov. 2008 were used to make microarrays and immunohistochemical staining for ER-alpha, E-CD, VEGF, MMP-2, MMP-9, and HIF-1alpha were performed. Clinicopathologic features of each immunohistochemical staining group were analyzed retrospectively. RESULTS: There is no immunohistochemistry staining in cases with benign thyroid lesions. The expression rate of ER-alpha, E-CD, VEGF, MMP-2, MMP-9, and HIF-1alpha in PTMC group was 66%, 58%, 82%, 66%, 71% and 63%, respectively. Bilateral tumor was statistically significant (48.0% vs 7.7%, P=0.015) related to MMP-2(+) PTMC group than in MMP-2(-) group. Bilateral tumor (44.4% vs 9.1%, P=0.060) and lymphovascular invasion (25.9% vs 0%, P=0.084) seemed to have greater relation to MMP-9(+) PTMC group than to MMP-9(-) group, but there is no statistically significant difference. Bilateral tumor (50.0% vs 7.1%, P=0.012), lymph node metastasis (45.8% vs 0%, P=0.003) and lymphovascular invasion (29.2% vs 0%, P=0.033) were significantly related to HIF-1alpha (+) PTMC group compared to HIF-1alpha(-) group. CONCLUSION: Our findings suggest that MMP-2, MMP-9 and HIF-1alpha expression could be used as a prognostic marker in PTMC. Larger studies are needed to assess its prognostic value in PTMC.