Expression of p53 and retinoblastoma gene in high-grade nodal peripheral T-cell lymphomas: Immunohistochemical and molecular findings suggesting different pathogenetic pathways and possible clinical implications

The expression of p53 and the retinoblastoma gene has been investigated by immunohistochemical and molecular analysis in 45 cases of nodal peripheral T-cell lymphoma with high-grade histology, Most cases (73.3 per cent) were primary nodal lymphomas without any extra-nodal site involvement. Most of t hem (75.6 per cent) were histologically classified as pleomorphic, small, m edium, and large cell type. Immunohistochemistry detected p53 in nine cases (20 per cent). In each of these cases, the polymerase chain reaction (PCR) /heteroduplex analysis did not show the presence of mutations, this finding being consistent with an alteration of the p53 functional pathway, in the presence of a wild-type protein. The retinoblastoma gene product was detect ed by immunohistochemistry in 35 cases (77.8 per cent) and not detected in ten cases (22.2 per cent). In the latter cases, the reverse transcription ( RT)-PCR analysis showed the presence of a specific retinoblastoma gene tran script in six cases and was negative in the remaining four cases. The immun ohistochemical and molecular findings seem to be consistent with abnormalit ies of retinoblastoma gene expression at either the transcriptional or the post-transcriptional level, Since all nine p53-positive cases by immunohist ochemical analysis were also retinoblastoma gene product-positive, and all ten retinoblastoma gene product-negative cases were also p53-negative, two different and mutually exclusive pathways of possible pathogenetic signific ance may be suggested, the former involving abnormalities of the functional pathway of p53 in the absence of mutations and the latter abnormalities of retinoblastoma gene expression at the transcriptional and/or post-transcri ptional level. Finally, the clinico-pathological correlations showed that p 53 immunohistochemical expression is significantly associated with a poorer response to intensive chemotherapy. Copyright (C) 1999 John Wiley & Sons, Ltd.