P53 AND P21(WAF1) EXPRESSION IN LYMPHOCYTIC THYROIDITIS AND THYROID-TUMORS

To clarify the roles of increased apoptosis and cell proliferation in chronic autoimmune lymphocytic thyroiditis and thyroid tumorigenesis, expression of p53 and p21(WAF1) proteins was immunohistochemically inv estigated in a series of 158 cases. Positive epithelial cells were qua ntified to give numbers per unit square and to score for distribution. They were found scattered in nontumorous thyroid tissue, their number s increasing with the severity of thyroiditis and the correlation betw een expression of the two proteins, regardless of the presence or abse nce of thyroid neoplasms. Simultaneous expression of both proteins was occasionally found in the same cells by analysis of serial histologic sections. In thyroid tumors, increased expression was found to be dif fuse, focal, or scattered for the distribution of p53- or p21(WAF1)-im munopositive cells in accordance with tumor cell dedifferentiation, sh owing significant correlation between expression of the two proteins. Correlated with these findings, enhanced apoptosis along, with decreas ed Bcl-2 expression and increased Ki-67 labeling in lymphocytic thyroi ditis and thyroid tumors was also confirmed in the same series, using in situ DNA nick-end labeling and immunohistochemical methods. Increas ed expression of p53 and/or p21(WAF1) proteins was thus suggestive of possible DNA damage and increased apoptosis in autoimmune thyroiditis. In addition, a significant correlation between protein overexpression and dedifferentiation of thyroid tumor cells was apparent. (C) 1998 A cademic Press.