Comparison of Molecular Changes in Lung Cancers in HIV-Positive and HIV-Indeterminate Subjects

Abstract

Context.-Human immunodeficiency virus (HIV) infection has been associated with an increasing incidence of malignancy, and HIV-infected persons have an increased incidence of primary lung carcinoma compared with the general population.Objective.-To investigate the molecular changes present in HIV-associated lung tumors and compare them with those present in lung carcinomas arising in HIV-indeterminate subjects ("sporadic 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 hospitals. Main Outcome Measures.-Analysis of frequency of loss of heterozygosity (LOH) and microsatellite alteration (MA) using polymerase chain reaction and 16 polymorphic microsatellite markers at 8 chromosomal regions frequently deleted in lung cancer. Presence of HIV and human papillomavirus (HPV) sequences.Results.-The overall frequency of LOH at all chromosomal regions tested and the frequencies at most of the individual regions were similar in the 2 groups. Frequency of MA present in the HIV-associated tumors (0.18) was 6-fold higher than in sporadic tumors (0.03) (PϽ.001). At least 1 MA was present in 10 (91%) of 11 HIV-associated tumors vs 17 (48%) of 35 sporadic tumors (P=.02). Molecular changes were independent of tumor stage and gender. HIV and HPV sequences were not detected in the HIV-associated lung carcinomas.Conclusions.-Microsatellite alterations, which reflect widespread genomic instability, occur at greatly increased frequency in HIV-associated lung carcinomas. Although the mechanism underlying the development of increased MAs is unknown, it may play a crucial role in the development of many HIV-associated tumors.

Sequential molecular abnormalities are involved in the multistage development of squamous cell lung carcinoma

“…Alterations in microsatellite size (microsatellite alterations) are present in many cancers, including lung carcinomas (Adachi et al, 1995;Fong et al, 1995;Mao et al, 1994;Merlo et al, 1994) and may re¯ect a form of genomic instability (Wistuba et al, 1998). We found MAs in 50% of the invasive tumors and in lesser percentages of histologically normal, preneoplastic and CIS foci.…”

HIV Infection in the Etiology of Lung Cancer: Confounding, Causality, and Consequences

“…HIV itself might have a direct oncogenic role. Although limited experimental data suggest that the HIV tat gene product may modulate expression of growth-related genes, amplification of HIV sequences in lung carcinoma tissue has not been demonstrated (55,56). Further, the limited data on risk for lung cancer associated with HIV RNA levels has not been suggestive of a strong association (4,36,41).…”

Single-institutional experience of clinicopathological analysis and treatment for lung cancer patients with human immunodeficiency virus infection

“…An immunocompromised state due to HIV infection is considered as the most critical risk factor for the occurrence of cancer, including lung cancer. Wistuba et al (20) reported that microsatellite alternations occurred at a six times higher rate in lung cancer specimens from patients with HIV infection compared with those without HIV, and that these genomic instabilities promote carcinogenesis. However, another clinical investigation demonstrated that increased HIV viral load or decreased CD4 + cell count is not associated with carcinogenesis (21).…”