bcl-2, p53 and proliferating cell nuclear antigen expression is related to the degree of differentiation in thyroid carcinomas

Abstract

Thyroid carcinomas are heterogeneous in terms of histology, clinical presentation, treatment response and prognosis. Since bcl-2 and p53 gene alterations are frequently involved in both lymphoid and epithelial malignancies, we analysed the expression of bcl-2, p53 and proliferating cell nuclear antigen (PCNA) in a group of 134 patients with thyroid neoplasms. The same markers were evaluated in fetal and adult normal thyroids as well as in 40 benign lesions. The study was carried out by immunocytochemistry on archival material using antibodies against bcl-2 and p53 protein on tissue sections of 40 adenomas (As), 20 medullary carcinomas (MCs), 70 well-differentiated carcinomas (WDCs), 20 poorly differentiated carcinomas (PDCs) and 24 undifferentiated carcinomas (UCs). bcl-2 immunoreactivity was detected in 36 out of 40 (90%) As, 20 out of 20 (100%) MCs, 60 out of 70 (85.7%) WDCs, 20 out of 20 (100%) PDCs, and 8 out of 24 (33.3%) of UCs. p53 expression was present in 11.4% of WDCs, 5% of PDCs, 5% of MCs and 62.5% of UCs. By contrast, no p53 immunoreactivity was detected in 40 adenomas and in all the normal thyroid tissues studied. We observed a positive correlation between the expression of p53 and PCNA (r = 0.42; P = 0.035) in a group of UCs, but not in WDCs, PDCs and MCs. Neither p53 nor bcl-2 expression were correlated with clinicopathological parameters, such as age, sex, pTNM and survival. Our results suggest that in tumours of the follicular epithelium p53 and bcl-2 protein abnormalities are associated with more advanced carcinomas and especially with undifferentiated carcinomas, while they are only rarely altered in tumours of the parafollicular C cells.