Aberrations in the fragile histidine triad(FHIT) gene may be involved in lung carcinogenesis in patients with chronic pulmonary tuberculosis.
It has been suggested that pulmonary tuberculosis (PT) is associated with lung carcinogenesis. To identify the genetic characteristics of precancerous PT lesions in lung, 20 patients were selected with a 1-month to 36-year history of PT and 20 lung cancer patients with a 2- to 53-year history of previous PT that had undergone lung resection at the Nanfang Hospital from 1999 to 2003; PCR-based microsatellite analysis with DNA extracted from microdissected tissues and immunohistochemical analysis of FHIT protein expression in samples of hyperplasia and cancer obtained from 40 patients were performed. Three microsatellite markers of the FHIT gene for loss of heterozygosity (LOH) analysis were used. LOH of the FHIT locus was frequently found among the lesions of hyperplasia and atypical hyperplasia obtained from 6 patients with a 1- to 36-year history of PT (12 of 30 informative lesions, 40%); none of 70 hyperplastic lesions obtained from 14 patients with a 1- to 11-month history of PT showed LOH at the FHIT gene; 17 of 20 (85%) cancer lesions obtained from 20 lung cancer patients with a 2- to 53-year history of previous PT showed LOH at the FHIT gene, which was significantly higher than hyperplasia and atypical hyperplasia obtained from patients with a 1- to 36-year history of PT in FHIT LOH (Fisher's exact test p = 0.003). Additionally, the level of FHIT protein expression was frequently reduced in the hyperplastic lung epithelial cells of PT with a 1- to 36-year history and cancer tissue. Our findings suggest that allelic loss of the FHIT gene may be involved in carcinogenesis in the lung of patients with PT.
Song
Lanying
L
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Yan
Wensheng
W
Deng
Min
M
Song
Shilin
S
Zhang
Jinhua
J
Zhao
Tong
T
D017766:Acid Anhydride Hydrolases / Q000235:genetics*; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002908:Chronic Disease; D004273:DNA, Neoplasm; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions; D012307:Risk Factors; D014397:Tuberculosis, Pulmonary / Q000150:complications*; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase