Transformation of follicular lymphoma. Expression of p53 and bcl-2 oncoprotein, apoptosis and cell proliferation

Transformation in follicular lymphoma represents an abrupt transition in tumor biology. The protein product of the bcl-2 oncogene is overexpressed in most follicular lymphomas and inhibits apoptosis. The protein product of the p53 oncogene prevents cell proliferation and induces apoptosis and is overexpressed in the dysfunctional (mutated) form. We studied 15 transformed lymphomas (large cell type), 7 follicular lymphomas before transformation and 2 control groups of follicular center cell lymphomas with no evidence of transformation (9 small cleaved cell and 10 de novo large cell lymphomas). High p53 expression (≥45% cells) was detected by immunostaining in 9/15 transformed lymphomas as compared with 0/10 de novo large cell lymphomas and 1/7 follicular lymphomas. Overexpression of bcl-2 (≥50% cells) was similar in transformed (11/15) and de novo large cell lymphomas (6/10). The apoptotic index was high (≥2%) in all transformed and large cell lymphomas and low in all follicular lymphomas and in the control group of small cleaved cell lymphomas. The apoptotic index in the transformed lymphomas appeared to be independent of bcl-2 expression and was sometimes paradoxically high in the presence of both p53 and bcl-2 overexpression. The apoptotic index was weakly associated with bcl-2 expression in de novo large cell lymphomas. Expression of p53 did not correlate with proliferation index. Our results indicate that p53 overexpression is a specific step associated with transformation and may occur shortly before it. This is not seen in de novo large cell lymphoma. Furthermore, the high apoptotic index in transformed lymphomas often occurs despite overexpression of bcl-2 and p53, implying that other factors may induce apoptosis in these tumors.