Decreased fragile histidine triad gene messenger RNA expression in lung cancer.
BACKGROUND
The fragile histidine triad (FHIT) gene is located at 3p14.2, a region frequently lost in various tumor types. Lack of FHIT expression has been found to occur frequently in multiple tumor types including lung cancer. We have investigated FHIT messenger RNA (mRNA) levels and other clinicopathologic data, including FHIT and p21 expression in lung cancer.


METHODS
The study included 97 lung cancer cases. The FHIT mRNA levels were quantified by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) using LightCycler.


RESULTS
The FHIT/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA levels were decreased in tumor tissues from lung cancer (13.844 +/- 33.047) compared with adjacent nonmalignant lung tissues (195.763 +/- 678.469; P < 0.0001). No significant difference in FHIT/GAPDH mRNA levels was found among age, T status, or lymph node metastasis. The FHIT/GAPDH mRNA level was less in squamous cell carcinoma (0.144 +/- 0.246), a smoking-related cancer, than in adenocarcinoma (0.72 +/- 1.321; P = 0.0355). FHIT/GAPDH mRNA levels were correlated with FHIT protein (P = 0.0139) and p21 protein (P = 0.0484) expression by immunohistochemistry. The prognosis for patients with lung cancer with low FHIT/GAPDH levels (< 0.26; n = 57) was significantly worse than in the patients with high FHIT/GAPDH levels (> 0.26; n = 40; log-rank test, P = 0.0404).


CONCLUSIONS
Using the LightCycler RT-PCR assay, decreased FHIT gene expression might occur early and play an important role in lung tumorigenesis and also correlate with the prognosis of lung cancer. However, further studies are needed to confirm the impact of FHIT in the biologic behavior of the tumor.
Sasaki
Hidefumi
H
Department of Surgery II, Nagoya City University Medical School, Nagoya, Japan. hisasaki@med.nagoya-cu.ac.jp
Haneda
Hiroshi
H
Yukiue
Haruhiro
H
Kobayashi
Yoshihiro
Y
Yano
Motoki
M
Fujii
Yoshitaka
Y
D017766:Acid Anhydride Hydrolases / Q000235:genetics*; D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000235:genetics / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D017931:DNA Primers; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D017931:DNA Primers; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000099170:Bis(5'-adenosyl)triphosphatase