DETECTION OF HIGH-MOBILITY GROUP-I HMGI(Y) PROTEIN IN THE DIAGNOSIS OF THYROID-TUMORS - HMGI(Y) EXPRESSION REPRESENTS A POTENTIAL DIAGNOSTIC INDICATOR OF CARCINOMA

Hyperplastic or neoplastic proliferative lesions of thyroid follicular epithelium consist of a spectrum, ranging from nodular hyperplasia to undifferentiated (anaplastic) carcinoma, and usually present as palpa ble thyroid nodules, Thyroid nodules are a common occurrence in the ge neral population, but only a small proportion of them are eventually d iagnosed as carcinoma. The difficulty in objectively identifying those thyroid nodules that are malignant to avoid unnecessary surgery, comb ined with the range and effectiveness of the available therapeutic opt ions in those patients who do, indeed, have thyroid carcinoma, has pro mpted the search for tumor markers and prognostic indicators. The high mobility group I (HMGI) proteins represent a class of nuclear protein s involved in the regulation of chromatin structure and function. HMGI (Y), one of the members of this class, is expressed at high levels dur ing embryogenesis and in malignant tumors but at generally low levels in normal adult human tissues. Previous work on a limited number of th yroid samples suggested that the detection of the HMGI(Y) proteins may provide a clinically useful diagnostic tool. To verify this assumptio n, we analyzed HMGI(Y) expression by a combination of immunohistochemi stry and reverse transcription-PCR in 358 thyroid tissue samples that were representative of the spectrum of thyroid tumor pathology, HMGI(Y ) was detectable in 18 of 19 follicular carcinomas, 92 of 96 papillary carcinomas, and II of 11 undifferentiated (anaplastic) carcinomas but in only 1 of 20 hyperplastic nodules, 44 of 200 follicular adenomas, and 0 of 12 normal tissue samples, The correlation between HMGI(Y) exp ression and a diagnosis of carcinoma was highly significant (P < 0.000 1), We also prospectively collected and analyzed for HMGI(Y) expressio n by immunohistochemistry and reverse transcription-PCR in 12 fine nee dle aspiration biopsies from 10 patients who subsequently underwent su rgical removal of a solitary thyroid nodule, HMGI(Y) was detectable on ly in the four fine needle aspiration biopsies, corresponding to the t hyroid nodules that were definitively diagnosed as carcinomas after su rgery (two follicular carcinomas and two papillary carcinomas). The re maining eight samples (six follicular adenomas and two samples consist ing of normal follicular cells) were negative. The findings of this st udy confirm the differential expression of HMGI(Y) in thyroid neoplasi a and indicate the HMGI(Y) protein as a potential marker for thyroid c arcinoma.