Chromosomal instability is a risk factor for poor prognosis of adenocarcinoma of the lung: Fluorescence in situ hybridization analysis of paraffin-embedded tissue from Korean patients.
BACKGROUND
In this study, we sought to evaluate the prognostic importance of chromosomal instability (CIN) in adenocarcinoma (AC) of the lung. The relationship between CIN detected by fluorescence in situ hybridization (FISH) and survival in AC patients was examined.


METHODS
Sixty-three surgical specimens of lung AC were analyzed. To identify tumors with CIN, p16 and multi-target DNA FISH assays for c-myc, chromosome 6, EGFR, and chromosome 5 (LAVysion, Vysis) were performed on nuclei extracted from paraffin-embedded tumor tissues. Survival rates were compared in terms of sex, age, histology, T factor, N factor, CIN, and smoking status. A sample was classified as CIN-positive if at least three of the five chromosomes were positive.


RESULTS
Out of the 63 specimens, 32 (39.7%) were CIN-positive. The 5-year overall disease-free survival rate was 58.7% as a whole, 46.9% for CIN-positive patients and 71.0% for the CIN-negative patients [hazard ratio (HR), 2.34; 95% confidence interval (CI), 1.04-5.26; p = 0.04]. The 5-year overall survival rate was 81.0%, 68.7% for CIN-positive patients and 93.5% for the CIN-negative patients (HR, 5.64; 95% CI, 1.23-25.70; p = 0.026). In multivariate analysis after adjusting for pathologic nodal staging, tumor staging, sex, age, and smoking history, compared with the CIN-negative patients, the CIN-positive status remained significantly associated with decreased overall survival (HR, 8.48; 95% CI, 1.66-43.42; p = 0.010).


CONCLUSIONS
CIN can be effectively detected in primary AC of lung using FISH analysis. CIN is associated with poor prognosis for AC, and may thus be utilized as an independent prognostic factor for the disease.
Choi
Chang-Min
CM
Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, South Korea.
Seo
Kwang Won
KW
Jang
Se Jin
SJ
Oh
Yeon-Mok
YM
Shim
Tae-Sun
TS
Kim
Woo Sung
WS
Lee
Dong-Soon
DS
Lee
Sang-Do
SD
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D043171:Chromosomal Instability; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007723:Korea; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D016612:Paraffin Embedding; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D012307:Risk Factors; D015996:Survival Rate
C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; C489427:MYC protein, human; D009363:Neoplasm Proteins; D016271:Proto-Oncogene Proteins c-myc; C512478:EGFR protein, human; D066246:ErbB Receptors