Ratio of metalloproteinase 2 to tissue inhibitor of metalloproteinase 2 in medullary thyroid carcinoma.
OBJECTIVE
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.


METHODS
Retrospective study of surgical samples.


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


METHODS
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.


METHODS
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.)


CONCLUSIONS
The ratio of MMP-2 to TIMP-2 expression is an additional and novel prognostic predictor of the outcome of medullary carcinoma treated surgically.
Cavalheiro
Beatriz Godoi
BG
Surgery Department of the Universidade de São Paulo Medical School, Rua Periquito 160-153, São Paulo, Brazil. bgcavalheiro@yahoo.com.br
Junqueira
Consuelo Rodrigues
CR
Brandão
Lenine Garcia
LG
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D018276:Carcinoma, Medullary / Q000201:enzymology*; D002648:Child; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D013964:Thyroid Neoplasms / Q000201:enzymology*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*
D014408:Biomarkers, Tumor; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2