Histopathologg 1992, 21, 331-334 p53 expression is common in malignant rnesothelioma G .KAFIRI, D.M.THOMAS, N. A.SHEPHERD*, T.KRAUSZ, D.P .LANE? zyx & P. A .HALL* Department of Histopathology,Royal Postgraduate Medical School, London and *Department zyxw of Histopathology. Gloucester Royal Hospital, Gloucester and zyxwvutsr tGll Transformation Research Group, CRC Laboratories, Department of Biochemistry, Dundee University, Dundee and $Department of Histopathology, UMDS, St Thomas's Hospital Campus, London, zyxwvut UK Date of submission 5 November 1991 Accepted for publication 1 May 1992 KAPIRI G.. THOMAS zyxwvutsrqp D.M., SHEPHERD N.A., KRAUSZ T., LANE D.P. & HALL P.A. (1992) Histopathology 21, 331-334 p53 expression is common in malignant mesothelioma The p53 tumour suppressor gene has been shown to be frequently mutated in a wide range of human neoplasms. This is accompanied by increased levels of p5 3 protein which become immunologically detectable in pathological material. We have investigated the possibility that the differential diagnosis between reactive and neoplastic mesothelium might be resolved using a polyclonal serum raised to human p53 protein, CM-1. None of 20 cases of reactive mesothelial proliferation showed p53 immunoreactivity while 70% (14 of 20) of cases of malignant mesothelioma showed p53 staining. We can thus infer that abnormalities of p53 appear to be a common event in malignant mesothelioma and that p53 immunostaining may be of value in the distinction of malignant mesothelioma from reactive hyperplasia. Keywords: tumour suppressor gene, p5 3, mesothelioma Introduction p5 3 is encoded by a tumour suppressor gene discovered by Lane & Crawford' as a consequence of its protein product binding to the SV40 virus large T antigen. For some time this nuclear protein was believed to have a role in neoplasia as a dominantly transforming oncopro- tein, but there is now considerable evidence pointing to p53 being a tumour suppressor genezs3. Mutation of p53 has been recently reported to be a frequent event in a range of human tumour types2e3, including breasP, stomach7,lung8v9, pancreas12,l i ~ e r ' ~ . ' ~ , uter- us7, brain and bladder cancerlo, melanoma', ovary and testis cancer15J6,and bone and soft tissue sarcomas17. The majority of abnormalities are mis-sense mutations that inactivate the tumour suppressor activity of p53, although growth promoting activity of mutant p53 has Address for correspondence: Professor P.A.Hal1. Department of Histopathology. UMDS, St Thomas's Hospital Campus, Lambeth Palace Road, London SEl 7EH. UK. also been des~ribed~.~. Wild type p53 has a very short half-life and is not detectable by immunological meth- ods. It has been consistently found that mutant protein, which takes on an abnormal conformation, is more stable, than wild type protein and accumulates in neoplastic ~ ells~.~.~.'~ to become immunologicallydetect- able. The identification of p53 may thus prove to be a useful marker of neoplasia in human pathological material19. The differential diagnosis between reactive mesothe- lial hyperplasia and malignant mesothelioma can fre- quently be difficult and is conventionally based upon a combination of clinical and morphological features such as papillary foci, necrosis, nuclear atypia and abnormal mitoses20*21. Immunohistochemical studies have in the past been advocated to assist with the differential diagnosis but have not been confirmed as being Consequently, we have investigated the possible diagnostic utility of employing the immunoloca- l i t i o n of p53 as an adjunct to morphology in the differential diagnosis of mesothelioma. 331