P53 PROTEIN ACCUMULATION AND THE PRESENCE OF HUMAN PAPILLOMAVIRUS DNAIN BRONCHIOLOALVEOLAR CARCINOMA CORRELATE WITH POOR-PROGNOSIS

Accumulation of the tumour suppressor gene p53 product due to a gene m utation is frequently seen in human carcinomas, including lung carcino ma. Another indirect mechanism involving p53 in malignant growth relat es to the E6 protein of the human papillomavirus (HPV), which is able to bind and degrade wild-type p53 protein, thus eliminating its tumour suppressor activities. Bronchiolo-alveolar carcinoma (BAG) is a rare type of lung carcinoma. The aim of our study was to examine the occurr ence of p53 accumulation and the presence of HPV DNA in BAG. Sections of 22 BACs were immunohistochemically stained using a p53 antibody, CM -1. The presence of HPV DNA in BACs was verified by in site hybridisat ion for HPV types 6, 11, 16, 18, 31 and 33 and confirmed by PCR. Thirt y-six percent of the tumours showed abnormal p53 nuclear accumulation, and HPV DNA, revealed by in site hybridisation, was found in 36%. Une xpectedly, only 13% of the type I BACs were positive for p53, whereas 45% of the type 2 BACs were positive. During a follow-up of 12-176 mon ths, only 10% of the patients with BACs negative for both p53 and HPV died of the disease, compared with 42% of the patients with either p53 or HPV positivity. No inverse relationship between abnormal p53 prote in accumulation and the presence of HPV DNA was found. (C) 1995 Wiley- Liss, Inc.