Is there a relationship between c-erbB-1 and c-erbB-2 amplification and protein overexpression in NSCLC?
In order to analyse the genetic abnormalities and protein expression of c-erbB-1 and -2, we have performed fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC) in resected non-small cell lung carcinoma (NSCLC). By IHC (106 patients), 11% of the patients were positive both for c-erbB-1 and -2 protein expression and 47% negative for both proteins. FISH (69 patients) showed a balanced disomy for both c-erbB-1 and -2 in 38%, all other cases had genetic abnormalities in at least one of both genes. c-erbB-2 gene was amplified in less than 10% of the tumours and c-erbB-1 gene was never amplified. c-erbB-2 protein overexpression was observed in only three out of the six cases showing c-erbB-2 amplification. The negative predictive value (NPV) of IHC for gene abnormalities was high for both markers. Median survival time (MST) was respectively of 76 and 174 weeks for patients with or without c-erbB-2 overexpression. Patients with c-erbB-2 amplification had a shorter survival: 125 weeks versus 165 weeks. MST was respectively of 109 and 196 weeks for patients with or without EGFR overexpression and patients with EGFR gene abnormalities had also a shorter survival with MST 136 weeks versus 189 weeks. These differences were not significant. In conclusion, if the majority of NSCLC showed genetic abnormalities in the c-erbB-1 and/or c-erbB-2 gene receptor, amplification could be observed only in a few tumours and was not strictly correlated with protein expression. Finally, survival of patients expressing EGFR and/or c-erbB-2 was slightly shorter.
Meert
Anne-Pascale
AP
Service des Soins Intensifs et Cancérologie Pulmonaire et Laboratoire d'Investigation Clinique et d'Oncologie Expérimentale HJ Tagnon, Institut Jules Bordet, 1 rue Héger Bordet, Bruxelles, Belgique. ap.meert@bordet.be
Martin
Benoit
B
Verdebout
Jean-Marc
JM
Noël
Sophie
S
Ninane
Vincent
V
Sculier
Jean-Paul
JP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D020869:Gene Expression Profiling; D018773:Genes, erbB-1; D018734:Genes, erbB-2; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis