: Genetic

We were interested in the article by Owen et al on p53 gene mutations in multiple myeloma. ' They had studied the p53 exons 5-9 by PCRSSCP and they found only one p53 mutation among 36 DNA samples from 31 patients with multiple myeloma. They concluded that p53 mutations are rare and confined to end stage leukaemic forms of the disease. We also studied p53 protein expression in myeloma cases determined by immunohistochemistry,2 and our results and conclusions were different from Owen and colleagues's. Our study group comprised 31 patients with multiple myeloma and four with isolated plasmacytoma. Twenty of the myeloma cases were newly diagnosed and the other 11 had relapsed or had resistant disease. All of the multiple myeloma patients were in stage III and 13 cases had also renal involvement. Fresh bone marrow aspiration samples from myeloma patients and paraffin wax embedded tissue sections from plasmacytoma cases were stained by the ABC method. To determine p53 protein expression, a monoclonal antibody against the p53 suppressor gene product (DO-7 Novacastra K-32; Novacastra, Newcastle upon Tyne, UK) recognising both normal and mutant forms of protein was used. Eight of the 35 cases showed p53 protein expression, none of the plasmacytomas showed p53 protein expression; therefore, p53 protein expression was found in 26% of cases of multiple myeloma. Four of the eight p53 positive cases were newly diagnosed and four of them were resistant and/or relapsed cases. Four of the 24 newly diagnosed, four of 11 relapsed cases, four of the 18 stage IIIA, and four of the 13 stage IIIB cases had p53 expression. There was no significant difference for p53 expression between newly diagnosed and relapsed cases, or between IIIA and IIIB cases (p < 0.25). None of our patients had features of leukaemic phase disease. p53 gene alterations in plasma cell dyscrasias have not been as well studied as other haematopoietic neoplasms, and the results of p53 alterations in multiple myeloma are limited but interesting. For example, p53 mutations have been found in eight of 10 multiple myeloma cell lines. This point was mentioned by Owen et al who speculated on the possibility of acquired occurrence in vitro.3 In clinical samples the frequency is between 3% and 50% depending on the methods used for detection. " Owen and colleagues did not give an account of the stage and status of the renal involvement for their patients. It is well known that p53 gene has a complex structure and that functional inactivation can result from the loss of p53 gene function. Therefore, there is no ideal method for the detection of p53 gene alterations; however, by using more than one technique such as immunohistochemistry and PCRSSCP, the results may be more informative. We believe that if immunocytochemistry could be used concurrently with PCR-SSCP analysis, Owen et al's results and comments might be more useful. We conclude that p53 mutations are not particularly rare in multiple myeloma. We agree that p53 mutation is not an initial step in myelomagenesis. We need larger studies with more patients and methods to determine the pathogenetic role of p53 mutations in multiple myeloma.