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Comparison of Molecular Changes in Lung Cancers in HIV-Positive and HIV-Indeterminate Subjects
Ignacio I. Wistuba, MD;
Carmen Behrens, MD;
Sara Milchgrub, MD;
Arvind K. Virmani, PhD;
Jaishree Jagirdar, MD;
Bilue Thomas;
Harry L. Ioachim, MD;
Leslie A. Litzky, MD;
Elisabeth M. Brambilla, MD;
John D. Minna, MD;
Adi F. Gazdar, MD
JAMA. 1998;279:1554-1559.
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) (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). 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.
From the Hamon Center for Therapeutic Oncology Research (Drs Wistuba, Behrens, Virmani, Minna, and Gazdar and Ms Thomas) and Departments of Pathology (Drs Milchgrub, Virmani, and Gazdar), Internal Medicine (Dr Minna), and Pharmacology (Dr Minna), University of Texas Southwestern Medical Center, Dallas; Departments of Pathology, Pontificia Universidad Catolica de Chile, Santiago (Dr Wistuba); Bellevue–New York University Medical Center, New York (Dr Jagirdar); Lenox Hill Hospital, New York, NY (Dr Ioachim); and University of Pennsylvania Medical Center, Philadelphia (Dr Litzky); and Department of Cellular Pathology, Regional Hospital Center Michallon, Grenoble, France (Dr Brambilla).
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