Immunohistochemical localization of p53 in human thyroid neoplasms: Correlation with biological behavior

Abstract

Molecular analyses of thyroid tumors have documented mutations in the tumor suppressor p53 gene almost exclusively in anaplastic carcinomas. In contrast, immunohistochemistry has localized p53 in differentiated papillary and follicular thyroid cancers. To establish the significance of p53 immunolocalization in these lesions, 78 thyroid tumors of follicular derivation were examined. All tumors were classified by strict criteria and the extent of tumor was determined morphologically. Immunohistochemical staining for p53 was performed on paraffin sections of formalin-fixed tumor tissue. The results of staining were correlated with diagnosis, tumor extent and clinical outcome. Immunopositivity for p53 was diffuse and strong in all five anaplastic carcinomas examined. There was no staining in five of six follicular adenomas. Four of nine follicular carcinomas had some degree of nuclear staining, but this was focal; all nine tumors were confined to the thyroid at the time of examination. Of 49 papillary carcinomas, 26 were intrathyroidal, and 7 of these were occult; there was no p53 positivity in any occult lesion and only S of the 19 palpable lesions stained. In contrast, among 23 papillary carcinomas with extra thyroidal extension or metastases, only 9 were negative for p53 immunoreactivity. Five of seven tall cell papillary carcinomas and one of two insular carcinomas had p53 immunopositivity and this correlated with aggressive behavior. These results support the tumorigenic role of p53 mutations postulated for anaplastic thyroid carcinomas and indicate that localization of p53 by immunohistochemistry is a useful prognostic index of clinical behavior in differentiated thyroid carcinomas of follicular cell derivation.

Expression of the melanoma-associated antigen is associated with progression of human thyroid cancer

“…Intragenic p53 mutations have been long recognized to be infrequent in primary human thyroid carcinomas (Ito et al 1992); they are associated with loss of differentiation and with the most aggressive tumors (Donghi et al 1993, Fagin et al 1993. Nevertheless, altered p53 immunoreactivity that may not reflect mutation has been described in several studies (Hosal et al 1997). The current study using a relatively large-sample size again demonstrated variable p53 immunoreactivity in thyroid carcinomas.…”

Prognostic value of epidermal growth factor receptor, p53 and galectin-3 expression in papillary thyroid carcinoma

“…However, p53 expression was observed in well-differentiated (10-18%) and poorly differentiated (40-80%) thyroid carcinomas, in one study. 31 Mutation and overexpression of p53 were observed more often in PTC when lymph node metastasis was present, 8 or when dedifferentiation to anaplastic carcinoma had occurred. 32,33 According to Hosal et al 8 and Godballe et al, 9 p53 expression is a significant independent prognostic indicator of PTC.…”

“…7 Immunohistochemical examination is typically performed not to diagnose follicular tumours of the thyroid gland, but rather to distinguish between types of follicular tumour; 6,7 such analysis is more helpful in predicting the patient's prognosis, rather than in confirming the diagnosis. Epidermal growth factor (EGFR) expression 8 and p53 expression 9 have been found to be significant independent prognostic factors for thyroid cancer. 10,11 The extent of surgery is generally chosen by analysis of risk factors (such as age, sex, extrathyroidal extension and radiation history), and total thyroidectomy is usually performed in those patients classified as high risk.…”

Lessons from Mouse Models of Thyroid Cancer

“…Another signaling pathway implicated in FTC is the phosphatidylinositol-3-kinase (PI3K)=AKT pathway, which is highlighted below and in Table 2. Other genetic alterations such as loss of p53 function and b-catenin activating mutation have been detected late in tumor development (63)(64)(65)(66).…”