CD97 - A DEDIFFERENTIATION MARKER IN HUMAN THYROID CARCINOMAS

CD97 is a dimeric glycoprotein of M-r 75,000-85,000 and 28,000 belongi ng to a novel subfamily of seven-span transmembrane region leukocyte c ell surface molecules. It is expressed abundantly in cells of hematopo ietic origin. This is the first report demonstrating the expression of CD97 outside the hematopoetic system. CD97 was studied in normal huma n and neoplastic follicular epithelium of the thyroid and anaplastic ( n = 3) and papillary (n = 1) thyroid carcinoma cell lines. In normal t hyroid tissue (n = 11), no immunoreactivity of CD97 could be found, wh ereas in differentiated thyroid carcinomas (n = 10), CD97 expression w as either lacking or low. Eleven of 12 undifferentiated anaplastic car cinomas revealed high CD97 presentation. CD97 was absent or only weakl y present in patients with postoperative T-1 tumors but increased grea tly with the progression to postoperative T-4 tumors. CD97 is clearly present in thyroid carcinoma cell lines but only at a very low level i n normal human thyrocytes. Quantitation of CD97 cell surface expressio n levels revealed that C 643 and SW 1736 cells showed a two to four ti mes higher specific antibody-binding capacity than did 8505 C and HTh 74 cells and a nearly 20 times higher specific antibody-binding capaci ty than normal thyrocytes. Phorbol 12-myristate 19-acetate treatment p rogressively caused a decrease of CD97 antigen expression in all cell lines to about 30% of their initial levels after 48 h. Immunohistochem ical staining of SW 1736 cells revealed that CD97 is located in most o f the cell compartments and suggested a CD97 internalization process a fter phorbol 12-myristate 13-acetate treatment. Semiquantitative rever se transcription-PCR showed a correlation of CD97 mRNA and cell surfac e CD97 expression level in the cell lines. SW 1736, HTh 74, and 8505 C cells apparently expressed CD97 with alternative glycosylation compar ed to peripheral lymphocytes, whereas most of the CD97 antigen present ed on thyrocytes and C 643 cells had glycosylation sites resembling th ose of lymphocytes. The data suggest that CD97 expression may be a sen sitive marker of dedifferentiation and of lymph node involvement in hu man thyroid tumors.