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Wistuba II, Behrens C, Milchgrub S, et al. Comparison of Molecular Changes in Lung Cancers in HIV-Positive and HIV-Indeterminate Subjects. JAMA. 1998;279(19):1554–1559. doi:https://doi.org/10.1001/jama.279.19.1554
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).
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.
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.
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.
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.
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.
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