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 investigated in a series of 158 cases. Positive epithelial cells were quantified to give numbers per unit square and to score for distribution. They were found scattered in nontumorous thyroid tissue, their numbers increasing with the severity of thyroiditis and the correlation between expression of the two proteins, regardless of the presence or absence 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 diffuse, focal, or scattered for the distribution of p53- or p21(WAF1)-immunopositive cells in accordance with tumor cell dedifferentiation, showing significant correlation between expression of the two proteins. Correlated with these findings, enhanced apoptosis along with decreased Bcl-2 expression and increased Ki-67 labeling in lymphocytic thyroiditis and thyroid tumors was also confirmed in the same series, using in situ DNA nick-end labeling and immunohistochemical methods. Increased 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.
School of Medicine, Kitasato University, Sagamihara, Kanagawa, 228, Japan. isaokaya@med.kitasato-u.ac.jp
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I
Okayasu
T
T
Osakabe
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M
Onozawa
T
T
Mikami
M
M
Fujiwara
D000906:Antibodies / Q000032:analysis; D017209:Apoptosis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis* / Q000276:immunology; D004791:Enzyme Inhibitors / Q000276:immunology / Q000378:metabolism*; D004847:Epithelial Cells / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D012720:Severity of Illness Index; D013964:Thyroid Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013967:Thyroiditis, Autoimmune / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000276:immunology
D000906:Antibodies; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53