PRESENCE OF HUMAN PAPILLOMAVIRUS DNA AND ABNORMAL P53 PROTEIN ACCUMULATION IN LUNG-CARCINOMA

Background - In some carcinomas inactivation of the tumour suppressor gene product p53, either by point mutation or indirectly by the human papillomavirus (HPV), has been suggested as two alternative routes to malignant transformation. To test this hypothesis in lung tumours, 43 lung carcinomas were analysed by in situ hybridisation and polymerase chain reaction (PCR) for the presence of HPV DNA, and the results were compared with p53 protein immunohistochemical analysis. Methods - The presence of HPV DNA in lung carcinoma was detected by nucleic acid in situ hybridisation for HPV types 6, 11, 16, 18, 31, and 33 using nonr adioactively labelled DNA probes. Polymerase chain reaction (PCR) anal ysis was performed on all cases showing positive HPV DNA labelling by in situ hybridisation and in an additional 13 negative cases. Abnormal nuclear accumulation of the p53 protein was revealed by immunohistoch emistry using the avidin-biotin-peroxidase complex method and a CM-1 p olyclonal anti-human p53 antibody and a monoclonal mutation-specific P ab 240 p53 antibody. Results - HPV DNA was found by in situ hybridisat ion in 13 lung carcinomas (30%). In all these cases subtype-specific H PV DNA could also be detected by PCR. Abnormal p53 protein accumulatio n was seen in 21 of the 43 carcinomas (49%), of which 18 were HPV nega tive. Twelve (57%) of the CM-1 positive cases were also positive for t he mutation-specific antibody Pab 240. There was an obvious inverse re lationship between the presence of papilloma viral DNA and abnormal p5 3 protein accumulation. Conclusions - p53 plays an important part in t he development of lung carcinomas and, in some cases, HPV may contribu te to it by binding and inactivating the p53 protein.