Relations of the c-myc gene and chromosome 8 in non-small cell lung cancer: analysis by fluorescence in situ hybridization.
BACKGROUND
Amplification of the c-myc gene has been reported in non-small cell lung cancer (NSCLC). We investigated the c-myc gene amplification and the numerical aberration of chromosome 8 by dual color fluorescence in situ hybridization (FISH) to evaluate the relation between possible genetic abnormalities, pathological factors and prognosis.


METHODS
Tumor tissue samples were obtained from 31 patients with NSCLC who underwent lobectomy with mediastinal lymph node dissection. Samples were analyzed by FISH using 8 alpha satellite DNA probe and c-myc gene cosmid probe. The relation between genetic abnormalities, pathological factors (T factor, tumor size, and N factor), and prognostic factors was evaluated by univariate and multivariate analysis, and by the Kaplan-Meier method and log-rank analysis.


RESULTS
Chromosome 8 aberrations were T1 (n=3), 44.0%; T2 (n=18), 35.7%; T3 (n=7), 40.0%; T4 (n=3), 39.7% (p=NS). The c-myc gene amplifications were T1, 54.3%; T2, 51.1%; T3, 51.0%; T4, 66.3% (p=NS). There was no difference between patients whose tumor was more than 5 cm (n=16), and 5 cm or less (n=15) in the rate of chromosome 8 aberration (39.3%: 36.3%), or the rate of the c-myc gene amplification (52.1%: 53.7%). N factors for chromosome 8 aberrations were N0 (n=18), 35.9%; and N2 (n=11), 44.9% (p=NS). In the c-myc gene amplification, there was a significant difference between N0 and N2 (48.6%, 61.3%, p=0.040). In univariate and multivariate analysis, chromosome 8 aberrations correlated with a poor prognosis (p=0.037 and p=0.041). The 5-year survival rate was 15.4% in patients whose rate of chromosome 8 aberrations was 40% or more (n=13), which was significantly less than that in patients with an aberration rate of less than 40% (n=19, 57.9%, p=0.014).


CONCLUSIONS
The c-myc gene amplification correlates with lymph node metastasis. Although there was no significant link between the amplification of the c-myc gene and clinical outcome, the numerical chromosome 8 aberrations was considered to be a factor for survival.
Kubokura
H
H
Department of Surgery II, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
Tenjin
T
T
Akiyama
H
H
Koizumi
K
K
Nishimura
H
H
Yamamoto
M
M
Tanaka
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D002869:Chromosome Aberrations / Q000401:mortality* / Q000502:physiology*; D025063:Chromosome Disorders; D002898:Chromosomes, Human, Pair 8 / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification / Q000502:physiology; D016259:Genes, myc / Q000502:physiology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D015996:Survival Rate