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Original Article
August 17, 2009

Ratio of Metalloproteinase 2 to Tissue Inhibitor of Metalloproteinase 2 in Medullary Thyroid Carcinoma

Author Affiliations

Author Affiliations: Surgery Department of the Universidade de São Paulo Medical School (Drs Cavalheiro, Junqueira, and Brandão) and Head and Neck Surgery Service of the Instituto Brasileiro de Controle do Câncer (Drs Cavalheiro and Brandão), São Paulo, Brazil.

Arch Otolaryngol Head Neck Surg. 2009;135(8):812-817. doi:10.1001/archoto.2009.92

Objectives  To develop an index for the ratio of metalloproteinase 2 (MMP-2) to its tissue inhibitor (TIMP-2) in immunostained medullary thyroid carcinoma specimens and to correlate it with clinical and pathologic prognostic factors. Metalloproteinases, enzymes related to the degradation of the extracellular matrix, take part in carcinogenesis and have been associated with the prognosis of neoplasias. Nevertheless, medullary carcinoma is rarely considered in research analysis. Researchers tend to favor the ratio of enzymes to their inhibitors over the absolute concentrations of these enzymes.

Design  Retrospective study of surgical samples.

Setting  Head and Neck Surgery and Endocrinology Departments, Universidade de São Paulo Medical School Hospital.

Patients  Surgical specimens from 33 patients who had been observed for a mean of 76.8 months (range, 4-201 months) were immunohistochemically stained for MMP-2 and TIMP-2. Only patients whose clinical and pathologic data were complete and whose specimens were preserved were included in the study.

Main Outcome Measures  The ratio between the expressions of MMP-2 and TIMP-2 was based on a staining index (immunostaining extent and intensity) of each of the markers.

Results  Proportionally large expressions of TIMP-2 over MMP-2 correlated with low occurrences of positive findings on initial cervical examination for the presence of thyroid nodules and/or lymphadenopathy (P = .02) and cervical lymph node metastases (P < .001), conditions correlated with prognosis. A correlation with cure at the end of follow-up (P = .01) was also observed. (P< .05 was considered statistically significant.)

Conclusion  The ratio of MMP-2 to TIMP-2 expression is an additional and novel prognostic predictor of the outcome of medullary carcinoma treated surgically.