Simultaneous expression of c-erbB-1, c-erbB-2, c-erbB-3 and c-erbB-4 receptors in non-small-cell lung carcinomas: correlation with clinical outcome.
The expression of c-erbB receptors was immunohistochemically examined in paraffin embedded specimens from non-small-cell lung carcinomas. A total of 209 patients were enrolled [squamous-cell carcinomas (n=59), adenocarcinomas (n=130), large-cell carcinomas (n=15) and giant-cell carcinomas (n=5)]. The HercepTest kit scoring guidelines were used for the interpretation of positivity. C-erbB-1 was overexpressed in older patients, in squamous-cell carcinomas and in poorly-differentiated tumours, whereas c-erbB-2 overexpression with adenocarcinomas and poorly-differentiated tumours. C-erbB-4 overexpression correlated with advanced disease stage. The c-erbB-1/4 pair was the most commonly overexpressed and significantly correlated with female gender, while the c-erbB-1/2 pair with older age. Response to chemotherapy was significantly reduced in patients with tumours overexpressing c-erbB-1 receptor as well as the c-erbB-1/2 and c-erbB-3/4 receptor pairs. Patients' overall survival was significantly correlated with the co-expression of c-erbB-1 and c-erbB-4 receptors. These findings clearly suggest that specific receptors overexpression or co-overexpression is correlated with patients' disease control rate and outcome. A better understanding of the overexpression of the heterodimerized partners of c-erbB family receptors may provide a useful predictive indicator of response to molecular targeted therapies with c-erbB inhibitors.
Koutsopoulos
Anastassios V
AV
Department of Pathology, University General Hospital of Heraklion, P.O. Box 1352, Heraklion 71110, Crete, Greece. akoutsop@med.uoc.gr
Mavroudis
Dimitris
D
Dambaki
Konstantina I
KI
Souglakos
John
J
Tzortzaki
Eleni G
EG
Drositis
John
J
Delides
George S
GS
Georgoulias
Vassilis
V
Stathopoulos
Efstathios N
EN
D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D012189:Retrospective Studies; D016019:Survival Analysis
D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases