COMPARISON OF MOLECULAR-CHANGES IN LUNG CANCERS IN HIV-POSITIVE AND HIV-INDETERMINATE SUBJECTS

Context.-Human immunodeficiency virus (HIV) infection has been associa ted with an increasing incidence of malignancy, and HIV-infected perso ns have an increased incidence of primary lung carcinoma compared with the general population,Objective.-To investigate the molecular change s present in HIV-associated lung tumors and compare them with those pr esent in lung carcinomas arising in HIV-indeterminate subjects (''spor adic tumors''). Design.-Convenience sample. Subjects.-Archival tissues from 11 HIV-positive persons and from 35 persons of indeterminate HIV status. Setting.-University-based medical centers and affiliated hosp itals. Main Outcome Measures.-Analysis of frequency of loss of heteroz ygosity (LOH) and microsatellite alteration (MA) using polymerase chai n reaction and 16 polymorphic microsatellite markers at 8 chromosomal regions frequently deleted in lung cancer. Presence of HIV and human p apillomavirus (HPV) sequences. Results.-The overall frequency of LOH a t all chromosomal regions tested and the frequencies at most of the in dividual regions were similar in the 2 groups, Frequency of MA present in the HIV-associated tumors (0.18) was 6-fold higher than in sporadi c tumors (0.03) (P<.001). At least 1 MA was present in 10 (91%) of 11 HIV-associated tumors vs 17 (48%) of 35 sporadic tumors (P=.02). Molec ular changes were independent of tumor stage and gender. HIV and HPV s equences were not detected in the HIV-associated lung carcinomas. Conc lusions.-Microsatellite alterations, which reflect widespread genomic instability, occur at greatly increased frequency in HIV-associated lu ng carcinomas, Although the mechanism underlying the development of in creased MAs is unknown, it may play a crucial role in the development of many HIV-associated tumors.