HER-2/neu overexpression in patients with radically resected nonsmall cell lung carcinoma. Impact on long-term survival.
BACKGROUND
Using immunohistochemistry, the authors prospectively investigated the expression of HER-2/neu protein in radically resected specimens of nonsmall cell lung carcinoma (NSCLC) and evaluated its impact on long-term prognosis.


METHODS
Between January 1991 and February 1992, surgical specimens from 130 consecutive patients who underwent radical resection for NSCLC (60 squamous cell carcinoma, 48 adenocarcinoma cases, and 22 large cell carcinomas) and that were staged (according to the TNM staging system) pathologically as Stage I (41 cases [32%]), Stage II (37 cases [28%]), and Stage IIIA (52 cases [40%]) were investigated for the expression of HER-2/neu using an avidin-biotin complex immunohistochemical technique. A semiquantitative four-stage grading system was used (0%, 1-5%, 6-20%, and > 20% positive cells) and an average number of 1500 cells/section was considered. Data were correlated with clinical and pathologic variables.


RESULTS
Normal bronchial tissue was found to be completely negative for HER-2/neu expression whereas 21 of the 130 tumor specimens (16%) were positive (range 1-> 20%). HER-2/neu positivity did not appear to differ significantly among pathologic stages and histotypes. Using a predetermined cutoff value of 5% positive cells, 15 tumor specimens (12%) were found to be above this value. The median survival time (85 weeks vs. 179 weeks) and overall survival rate were significantly lower in patients with > 5% HER-2/neu-positive tumors (hazard ratio for the group with > 5% positive cells: 2.94, 95% confidence interval, 1.62-5.34; P < 0.0004). On multivariate analysis, HER-2/neu and extent of tumor emerged as independent factors for disease-related mortality.


CONCLUSIONS
In NSCLC, the negative impact of HER-2/neu overexpression on survival was maintained in the long-term follow-up of radically resected patients. HER-2/neu overexpression may be a valuable prognostic factor as well as a potential target for biologic therapies.
Selvaggi
Giovanni
G
Department of Clinical and Biological Sciences, University of Torino, Azienda Ospedaliera S. Luigi, Regione Gonzole, 10, 10043 Orbassano, Torino, Italy.
Scagliotti
Giorgio V
GV
Torri
Valter
V
Novello
Silvia
S
Leonardo
Eugenio
E
Cappia
Susanna
S
Mossetti
Claudio
C
Ardissone
Francesco
F
Lausi
Paolo
P
Borasio
Piero
P
D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000601:surgery; D000328:Adult; D000368:Aged; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000401:mortality / Q000601:surgery; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality / Q000601:surgery; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D015996:Survival Rate
D018719:Erb-b2 Receptor Tyrosine Kinases