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Matrix metalloproteinase (MMP) expression by differentiated thyroid carcinoma of children and adolescents

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Abstract

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.

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Authors and Affiliations

  1. Department of Pediatrics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, MD, 20814, USA

    A. Patel, A. M. Straight, H. Mann, E. Duffy, C. Fenton, C. Dinauer &  G. L. Francis

  2. Department of Pediatrics, Walter Reed Army Medical Center, Washington, DC, USA

    A. M. Straight, C. Fenton, C. Dinauer &  G. L. Francis

  3. Department of Clinical Investigation, Walter Reed Army Medical Center, Washington, DC, USA

    C. Dinauer

  4. Department of Endocrinology, Memorial Sloan Kettering Cancer Center, NY, NY, USA

    R. M. Tuttle

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  1. A. Patel
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  2. A. M. Straight
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  3. H. Mann
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  4. E. Duffy
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  5. C. Fenton
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  6. C. Dinauer
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  8. G. L. Francis
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Correspondence to G. L. Francis.

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The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or to reflect the opinions of the Uniformed Services University of the Health Sciences, the Department of the Army, or the Department of Defense.

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Patel, A., Straight, A.M., Mann, H. et al. Matrix metalloproteinase (MMP) expression by differentiated thyroid carcinoma of children and adolescents. J Endocrinol Invest 25, 403–408 (2002). https://doi.org/10.1007/BF03344028

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