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

• Published in: The Journal of pathology Vol. 188; no. 4; pp. 400 - 406
• Main Authors: Pescarmona, Edoardo, Pignoloni, Patrizia, Santangelo, Carmela, Naso, Giuseppe, Realacci, Massimo, Cela, Olga, Lavinia, Anna Maria, Martelli, Maurizio, Russo, Matteo A., Baroni, Carlo D.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-08-1999; Wiley
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Biomarkers, Tumor - metabolism; Cell Division; Female; Gene Expression; Genes, p53; Genes, Retinoblastoma; Hematologic and hematopoietic diseases; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, T-Cell, Peripheral - drug therapy; Lymphoma, T-Cell, Peripheral - genetics; Lymphoma, T-Cell, Peripheral - metabolism; Male; Medical sciences; Middle Aged; Neoplasm Proteins - metabolism; p53; peripheral T-cell lymphoma; retinoblastoma gene; Retinoblastoma Protein - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Treatment Outcome; Tumor Suppressor Protein p53 - metabolism; Antineoplastic agent; Human; Immunohistochemistry; Retinoblastoma gene; Reverse transcription; Malignant hemopathy; Non Hodgkin lymphoma; Gene expression; Carcinogenesis; Peripheral T cell lymphoma; Polymerase chain reaction; Response; Pathology; TP53 Gene; Treatment; Lymphoproliferative syndrome; Molecular biology; Tumor suppressor gene; High malignancy
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/(SICI)1096-9896(199908)188:4<400::AID-PATH379>3.0.CO;2-#

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 them (75·6 per cent) were histologically classified as pleomorphic, small, medium, 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 detected 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 transcript in six cases and was negative in the remaining four cases. The immunohistochemical and molecular findings seem to be consistent with abnormalities of retinoblastoma gene expression at either the transcriptional or the post‐transcriptional level. Since all nine p53‐positive cases by immunohistochemical 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 significance may be suggested, the former involving abormalities 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‐transcriptional level. Finally, the clinico‐pathological correlations showed that p53 immunohistochemical expression is significantly associated with a poorer response to intensive chemotherapy. Copyright © 1999 John Wiley & Sons, Ltd.