The factor(s) that control
metastasis of
thyroid carcinoma are unknown, but the
matrix metalloproteinases (
MMPs) are excellent candidates. MMP-1, membrane-type-1
MMP (MT1-MMP), and tissue inhibitor of MMP-1 (TIMP-1) have all been implicated, but the site of production and importance are disputed. In vitro, normal thyroid cells secrete
TIMP-1, while
thyroid cancer cells secrete
TIMP-1 and MMP-1. However, previous pathological studies identified MMP-1 and
TIMP-1 only in the stroma surrounding
thyroid carcinoma. These data suggest that
thyroid carcinoma or
tumor-associated inflammatory cells might secrete
a factor(s) which stimulates MMP-1 or
TIMP-1 expression by surrounding tissues. We hypothesized that MMP-1,
MT1-MMP, and
TIMP-1 would be directly expressed by
thyroid carcinoma and might promote invasion or
metastasis. We used immunohistochemistry to determine the expression of MMP-1,
MT1-MMP, and
TIMP-1 in 32
papillary thyroid carcinoma (PTC), 10
follicular thyroid carcinoma (
FTC) and 13 benign thyroid lesions from children and adolescents. The intensity of staining was graded from absent (grade 0) to intense (grade 3). Average MMP-1 expression (mean relative intensity units+/-SE) was significantly greater among PTC (1.97+/-0.15; p=0.004) and
FTC (2.2+/-0.25; p=0.006) compared to benign lesions (1.30+/-0.15); but there was no relationship between MMP-1 expression and invasion,
metastasis, or recurrence. Expression of
MT1-MMP and
TIMP-1 was similar for benign and malignant lesions; but recurrent PTC expressed lower levels of
TIMP-1 when compared to non-recurrent PTC (p=0.049). Only the expression of
TIMP-1 correlated with the presence of
tumor-associated lymphocytes (r=0.35, p=0.032). We conclude that MMP-1,
MT1-MMP and
TIMP-1 are all expressed by
thyroid carcinoma and could be important in promoting recurrence.