Comparison of molecular changes in lung cancers in HIV-positive and HIV-indeterminate subjects.
BACKGROUND
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").


METHODS
Convenience sample.


METHODS
Archival tissues from 11 HIV-positive persons and from 35 persons of indeterminate HIV status.


METHODS
University-based medical centers and affiliated hospitals.


METHODS
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.
Wistuba
I I
II
Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas 75235-8593, USA.
Behrens
C
C
Milchgrub
S
S
Virmani
A K
AK
Jagirdar
J
J
Thomas
B
B
Ioachim
H L
HL
Litzky
L A
LA
Brambilla
E M
EM
Minna
J D
JD
Gazdar
A F
AF
D000328:Adult; D004273:DNA, Neoplasm / Q000032:analysis*; D004279:DNA, Viral / Q000032:analysis; D006678:HIV / Q000235:genetics; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000150:complications* / Q000235:genetics / Q000473:pathology* / Q000821:virology; D018895:Microsatellite Repeats; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics; D016133:Polymerase Chain Reaction
D004273:DNA, Neoplasm; D004279:DNA, Viral