Is the aberrant expression of p53 by immunocytochemistry a surrogate marker of TP53 mutation and/or deletion in chronic lymphocytic leukemia?

To the Editor We read with interest the article by Chang et al 1 in which the aberrant expression of nuclear p53 detected by immunohistochemical analysis in 10% or more of bone marrow biopsy cells of 14 of 110 patients affected by chronic lymphocytic leukemia (CLL) identified all but 1 case with del(17p) in 10% or more of cells by fluorescent in situ hybridization (FISH). Deletion of chromosome 17p13 occurs in 5% to 7% of untreated CLLs and in 20% to 30% of relapsed or resistant cases 2 and is strongly associated with TP53 mutations of the remaining allele; however, in 3% to 4.5% of cases, the TP53 mutation is not associated with the deletion, but it still maintains its adverse prognostic value. 3,4 TP53 mutations lead to an accumulation of an abnormal prolonged half-life p53 protein, which can be detected by immunohistochemical or immunocytochemical analysis. 1,5,6 In CLL, the detection of TP53 alterations is strongly associated with an aggressive disease resistant to therapy and overall poor survival. 7-9 It is so far the only biologic parameter that can direct the choice of treatment and the indication for allogeneic stem cell transplantation. 10 Owing to the importance of a rapid and reliable screening of TP53 status in patients with CLL, we evaluated a cohort of 440 CLL cases (36% at diagnosis, 53% at first progression, 11% relapsed/resistant) for TP53 dysfunction combining 2 different methods: direct sequencing of TP53 exons 5 to 8 by polymerase chain reaction and p53 detection by immunocytochemical analysis on peripheral blood cells, as previously described. 6,11 The anti-p53 monoclonal antibody (DO-7, DAKO, Glostrup, Denmark) was the same used by Chang et al. 1 In a subgroup of 300 patients, del(17p) by FISH was also assessed, as previously described. 12 Of the 440 cases analyzed, 19 (4.3%) were found to have p53 protein expression in 10% or more of circulating cells and 35 (8.0%) harbored a TP53 mutation; of the 300 cases evaluated by FISH, 27 (9.0%) had del(17p) in 10% or more of the cells. Cases immunocytochemically positive for p53 carried a mutated TP53 in 10 cases and were wild-type in 9; immunocytochemically negative cases carried a mutated TP53 in 25 cases and were wild-type in 396. Thus, the sensitivity and specificity of p53 protein assessment by immunocytochemical analysis to detect a TP53 mutation were 29% and 98%, respectively; the positive predictive value (PPV) and negative …