TY - JOUR
T1 - HER-2/neu overexpression in patients with radically resected nonsmall cell lung carcinoma
T2 - Impact on long-term survival
AU - Selvaggi, Giovanni
AU - Scagliotti, Giorgio V.
AU - Torri, Valter
AU - Novello, Silvia
AU - Leonardo, Eugenio
AU - Cappia, Susanna
AU - Mossetti, Claudio
AU - Ardissone, Francesco
AU - Lausi, Paolo
AU - Borasio, Piero
PY - 2002/5/15
Y1 - 2002/5/15
N2 - 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.
AB - 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.
KW - HER-2/neu
KW - Nonsmall cell lung carcinoma
KW - Overexpression
KW - Prognosis
KW - Radical resection
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U2 - 10.1002/cncr.10531
DO - 10.1002/cncr.10531
M3 - Article
C2 - 12173335
AN - SCOPUS:0037093969
VL - 94
SP - 2669
EP - 2674
JO - Cancer
JF - Cancer
SN - 0008-543X
IS - 10
ER -