BCL-2 PROTEIN EXPRESSION IN CARCINOMAS ORIGINATING FROM THE FOLLICULAR EPITHELIUM OF THE THYROID-GLAND

The bcl-2 product has been related to the block of programmed cell dea th (apoptosis) both in lymphoid and in epithelial cells. The pathologi cal expression of bcl-2 has been investigated mainly in haematological malignancies. Here we have investigated bcl-2 expression in a model o f epithelial tumours represented by the spectrum of carcinomas arising from the follicular epithelium of the human thyroid gland. The analys is was carried out by immunocytochemistry on archival material using m onoclonal antibodies against bcl-2 and thyroglobulin (Tg) on consecuti ve sections of 94 well-differentiated carcinomas (WDCs), 19 poorly dif ferentiated carcinomas (PDCs), and 22 undifferentiated carcinomas (UCs ) of the thyroid gland. In a subset of 5 cases of UC showing a differe ntiated component (UC-D), the expression of p53 protein was also inves tigated. As controls, fetal and adult normal thyroid glands and adenom as were analysed. bcl-2 expression was detected in 74 of 94 cases (78. 7 per cent) of WDC, 16 of 19 cases (84.2 per cent) of PDC, and 3 of 22 cases (13.6 per cent) of UC. Simultaneous expression of bcl-2 protein and Tg was observed in 74 of 94 cases (78.7 per cent) of WDC, 13 of 1 9 cases (68.4 per cent) of PDC, and in no case of UC. bcl-2 and Tg imm unostaining was detected in all fetal and normal thyroid glands as wel l as in the adenoma specimens examined. In the subset of UC-D, mutual exclusion of bcl-2 and p53 expression was observed in the undifferenti ated and differentiated components (p53 but not bcl-2 expressed in the former). Our data indicate that within the spectrum of thyroid carcin omas bcl-2 expression, similarly to Tg, is strictly correlated with ce ll differentiation and that its abrogation is restricted to UCs, in wh ich alterations of the p53 gene represent a late genetic event related to tumour progression.