Background. The Id-1 helix-loop-helix protein inhibits differentiation and enhances cell proliferation. It is required for cell cycle progression. The Id-1 gene is highly expressed in a variety of tumor-derived cell lines. It increases after mitogen stimulation and is overexpressed in some human neoplasms. Therefore, we hypothesized that the Id-1 gene may play a role in medullary thyroid carcinogenesis. Methods. The expression of the Id-1 protein in human medullary thyroid cancer (MTC) and the corresponding normal thyroid tissue was determined by Id-1 immunohistochemistry. In a human MTC cell line (TT), the effects of growth stimulation and redifferentiation on Id-1 expression were determined by Northern blot analysis. Results. Id-1 immunostaining intensity in 9 MTC samples (6 sporadic, 2 familial, and 1 MEN 2A) was moderate to strong. However, it was absent or faint in the corresponding normal thyroid tissue. The Id-1 protein was significantly overexpressed in MTC compared with corresponding normal thyroid tissue on the basis of the percentage of positive cells and immunostaining intensity (P =.002). In the TT cell line, Id-1 messenger RNA (mRNA) expression was increased 4-fold after growth stimulation with serum. Phorbol ester (which induces redifferentiation in the TT cell line) downregulated Id-1 mRNA expression. Conclusions. Id-1 is overexpressed in MTC. The Id-1 gene may play a role in the regulation of MTC differentiation and proliferation. (Surgery 2000;128:952-7.)
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*Supported by an NIH T32 training grant in surgical oncology basic science.
**Reprint requests: Electron Kebebew, MD, University of California, San Francisco, Department of Surgery, 513 Parnassus, S-343, San Francisco, CA 91434-0470.
© 2000 Mosby, Inc. Published by Elsevier Inc. All rights reserved.