HER-2/neu overexpression in patients with radically resected nonsmall cell lung carcinoma: Impact on long-term survival

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. Between January 1991 and February 1992, surgical specimens from 130 consecut...

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Published in:Cancer 2002-05, Vol.94 (10), p.2669-2674
Main Authors: SELVAGGI, Giovanni, SCAGLIOTTI, Giorgio V, TORRI, Valter, NOVELLO, Silvia, LEONARDO, Eugenio, CAPPIA, Susanna, MOSSETTI, Claudio, ARDISSONE, Francesco, LAUSI, Paolo, BORASIO, Piero
Format: Article
Language:English
Subjects:
Adenocarcinoma - genetics
Adenocarcinoma - mortality
Adenocarcinoma - surgery
Adult
Aged
Biological and medical sciences
Carcinoma, Large Cell - genetics
Carcinoma, Large Cell - mortality
Carcinoma, Large Cell - surgery
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - mortality
Carcinoma, Non-Small-Cell Lung - pathology
Carcinoma, Non-Small-Cell Lung - surgery
Carcinoma, Squamous Cell - genetics
Carcinoma, Squamous Cell - mortality
Carcinoma, Squamous Cell - surgery
Female
Histocytochemistry
Humans
Lung Neoplasms - genetics
Lung Neoplasms - mortality
Lung Neoplasms - pathology
Lung Neoplasms - surgery
Male
Medical sciences
Middle Aged
Pneumology
Prognosis
Prospective Studies
Receptor, ErbB-2 - analysis
Survival Rate
Tumors of the respiratory system and mediastinum
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Summary: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. 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. 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. 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.
ISSN:0008-543X
1097-0142
DOI:10.1002/cncr.10531