POSTTHYMIC T-CELL LYMPHOMAS FREQUENTLY OVEREXPRESS P53 PROTEIN BUT INFREQUENTLY EXHIBIT P53 GENE-MUTATIONS

We recently demonstrated that only one of 36 T-cell neoplasms containe d p53 gene mutations. AL though p53 gene mutations are known to result in overexpression of the p53 gene product, we also recently discovere d that p53 protein overexpression does not correlate with p53 gene mut ations, but does correlate with proliferation (r = 0.92), in anaplasti c large cell lymphoma. In view of these findings, we investigated 34 n on-human T-cell lymphotropic virus type I (HTLV-I) related postthymic T-cell lymphomas immunohistochemically for p53 protein, using monoclon al antibody 1801, and for proliferation, using monoclonal antibody Ki- 67, and quantitated the results with the CAS-200 computerized image an alysis system. We evaluated the presence of mutations in conserved exo ns 5 to 9 of the p53 gene using single-strand conformation polymorphis m analysis and DNA sequencing. p53 mutations were detected in three of 34 cases, including two that contained deletions. p53 protein overexp ression was detected in 17 of 34 cases, including the three mutated ca ses, with reactivities ranging from 10% to 48%. However, many cases il l which a structural alteration could not be detected demonstrated lev els of p53 protein expression comparable to those cases that were muta ted. Correlation of p53 protein expression and proliferation, as asses sed by Ki-67 expression, in this group of lymphomas was poor (r = 0.34 ). Whether alternative mechanisms of p53 protein inactivation are caus ing phenotypic overexpression of the p53 protein in these malignant ly mphomas is unknown, although preliminary studies do not support a majo r role for such mechanisms. Therefore, the etiology and the significan ce of p53 protein overexpression in the cases that lack a demonstrable mutation is unclear Nevertheless, as in anaplastic large cell lymphom a, overexpression of the p53 gene product is not a reliable predictor of the presence of mutations in conserved portions of the p53 gene in non-HTLV-I associated post-thymic T-cell lymphoma.