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 nonradioactively labelled DNA probes. Polymerase chain reaction (PCR) analysis 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 immunohistochemistry using the avidin-biotin-peroxidase complex method and a CM-1 polyclonal anti-human p53 antibody and a monoclonal mutation-specific Pab 240 p53 antibody.


RESULTS
HPV DNA was found by in situ hybridisation in 13 lung carcinomas (30%). In all these cases subtype-specific HPV DNA could also be detected by PCR. Abnormal p53 protein accumulation was seen in 21 of the 43 carcinomas (49%), of which 18 were HPV negative. Twelve (57%) of the CM-1 positive cases were also positive for the mutation-specific antibody Pab 240. There was an obvious inverse relationship between the presence of papilloma viral DNA and abnormal p53 protein accumulation.


CONCLUSIONS
p53 plays an important part in the development of lung carcinomas and, in some cases, HPV may contribute to it by binding and inactivating the p53 protein.
Soini
Y
Y
Department of Pathology, University of Oulu, Finland.
Nuorva
K
K
Kamel
D
D
Pöllänen
R
R
Vähäkangas
K
K
Lehto
V P
VP
Pääkkö
P
P
D000230:Adenocarcinoma / Q000150:complications / Q000378:metabolism / Q000821:virology*; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000378:metabolism / Q000821:virology*; D004247:DNA; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008175:Lung Neoplasms / Q000150:complications / Q000378:metabolism / Q000821:virology*; D008969:Molecular Sequence Data; D009154:Mutation; D027383:Papillomaviridae / Q000145:classification / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications; D016133:Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000302:isolation & purification*; D014412:Tumor Virus Infections / Q000150:complications
D016159:Tumor Suppressor Protein p53; D004247:DNA