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Study of pretreatment serum levels of HER‐2/ neu oncoprotein as a prognostic and predictive factor in patients with advanced nonsmall cell lung carcinoma
Author(s) -
Ardizzoni Andrea,
Cafferata Mara A.,
Paganuzzi Michela,
Filiberti Rosangela,
Marroni Paola,
Neri Monica,
Fontana Vincenzo,
Nicoló Guido,
Perdelli Luisa,
Stampino Corrado Gallo,
Rosso Riccardo,
Puntoni Riccardo
Publication year - 2001
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(20011001)92:7<1896::aid-cncr1707>3.0.co;2-0
Subject(s) - medicine , histology , stage (stratigraphy) , lung , carcinoma , gastroenterology , immunohistochemistry , lung cancer , oncology , chemotherapy , pathology , biology , paleontology
BACKGROUND HER‐2/ neu tissue overexpression is found in nearly 15% of patients with nonsmall cell lung carcinoma and is reported to affect prognosis adversely in surgical series. However, the prognostic role of serum HER‐2/ neu oncoprotein, particularly in patients with advanced lung carcinoma, remains unknown. This study was designed to assess the potential value of measuring serum levels of HER‐2/ neu oncoprotein in predicting response to treatment and survival in patients with locally advanced and metastatic nonsmall cell lung carcinoma. METHODS Baseline serum HER‐2/ neu levels (fm/mL) were studied using an enzyme‐linked immunosorbent assay method in 84 patients with newly diagnosed, advanced nonsmall cell lung carcinoma who underwent chemotherapy. RESULTS The patients enrolled in the study included 76 males and 8 females, with a median age of 62 years (range, 36–73 years) and a median performance status of 1. Fifty patients (59.5%) had nonsquamous histology, and 34 patients (40.5%) had squamous cell carcinoma. Thirty‐four patients (40.5%) had Stage III disease, and 50 patients (59.5%) had Stage IV disease. The mean baseline value of HER‐2/ neu in the whole series was 56.1 fm/mL (range, 13.0–103.8 fm/mL). HER2 immunohistochemistry on paraffin embedded tissue was performed in 18 patients. HER‐2/ neu tissue overexpression was found in only one patient, who also showed high serum levels (102 fm/mL). No correlation was observed between protein serum quantitation and gender, age, histology, stage, performance status, leukocyte count, or smoking. Nonresponding and responding patients exhibited similar oncoprotein levels (median, 57.6 fm/mL vs. 51.9 fm/mL, respectively). The overall survival rate was 42.5% at 1 year and 12% at 2 years, with a median survival duration of 10 months. At univariate analysis, high HER‐2/ neu serum levels were associated with an unfavorable survival outcome. Using a cut‐off point for HER‐2/ neu of 73.0 fm/mL (corresponding to the 80th percentile of protein concentration), the survival of patients who had higher serum levels of HER‐2/ neu was significantly worse compared with patients who had lower serum levels (median, 7.1 months vs. 10.9 months; P = 0.004). Multivariate analysis confirmed the independent predictive value of serum HER‐2/ neu concentration as a negative prognostic factor ( P = 0.02). CONCLUSIONS High pretreatment levels of HER‐2/ neu oncoprotein are associated with an adverse prognostic impact on survival in patients with locally advanced or metastatic nonsmall cell lung carcinoma. Cancer 2001;92:1896–904. © 2001 American Cancer Society.