IMMUNOCHEMICAL ANALYSIS OF THE P53 ONCOPROTEIN IN MATCHED PRIMARY AND METASTATIC HUMAN TUMORS

There is much interest in the range of genetic aberrations which occur in human malignancies. An immunohistochemical study has been carried out to investigate the consistency of expression of abnormally accumulated p53 protein in paired samples of archival primary and metastatic carcinomas. The staining of methacarn-fixed tissue from 136 matched pairs of mammary carcinoma and 20 cancers from other sites was completed using antibody CM-1 and DO1 in a sensitive peroxidase-conjugated streptavidin-biotin technique. The majority of tumour cells were positive in 25% and the tumours were negative in 17% of the primary carcinomas; staining was heterogeneous in the remaining cases. Staining was identical in 180/186 (96%) metastatic lesions. An ELISA assay carried out on 12 matched pairs of the tumour specimens demonstrated that altered conformation of the aberrant p53 protein present in a primary lesion was maintained in its metastasis. These data indicate that alterations in the p53 gene result in a relatively stable phenotype and that progression of disease is not usually accompanied by either further mutation or loss of the mutant allele.