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c‐erbB‐2 Expression in small‐cell lung cancer is associated with poor prognosis
Author(s) -
Micke Patrick,
Hengstler Jan Georg,
Ros Roser,
Bittinger Fernando,
Metz Tsegay,
Gebhard Susanne,
Beeh Kai Michael,
Oesch Franz,
Buhl Roland
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.1229
Subject(s) - medicine , stage (stratigraphy) , enolase , chemotherapy , immunohistochemistry , hazard ratio , erbb , lung cancer , oncology , log rank test , cancer , tyrosine kinase inhibitor , survival analysis , lactate dehydrogenase , biology , confidence interval , enzyme , paleontology , biochemistry
Small‐cell lung cancer (SCLC) carries a bad prognosis despite good initial response to chemotherapy. It is therefore important to identify molecular markers that influence survival as potential new therapeutic targets. In our study, expression of the tyrosine kinase c‐erbB‐2 (HER2/neu) receptor in tumor tissues of 107 consecutive newly diagnosed patients with primary SCLC was quantified using a monoclonal antibody directed against the c‐terminal domain of c‐erbB‐2 . A clear‐cut positive expression of c‐erbB‐2 was observed in 13% of patients. Surprisingly, c‐erbB‐2 was an independent prognostic factor (RR = 2.16; p = 0.014) when a proportional‐hazard model was adjusted to stage (limited vs. extensive disease) and performance status (WHO I–IV), the most relevant clinical parameters. Similarly, a significant association between c‐erbB‐2 and survival was obtained if a larger number of clinical parameters were included into the analysis, namely response to chemotherapy, TNM stage, lactate dehydrogenase (LDH), neuron‐specific enolase (NSE), gender and age ( p = 0.033). Interestingly, c‐erbB‐2 expression was more relevant for patients with advanced tumors. In the subgroup of patients with bad performance status (WHO II–IV), median survival of patients with undetectable c‐erbB‐2 expression was 274 days compared with only 23 days for patients with clear‐cut positive c‐erbB‐2 immunohistochemistry ( p = 0.0031; log‐rank test). Similar results were obtained for patients with extensive disease ( p = 0.028) and high TNM stages (T>2 or N>1 or M1; p < 0.068, all comparisons). In contrast, c‐erbB‐2 expression was not associated with survival in patients with limited disease ( p = 0.97), low TNM stages ( p > 0.56, all comparisons) and good performance status ( p = 0.97). In conclusion, c‐erbB‐2 is expressed in more than 10% of SCLC. Expression of c‐erbB‐2 is an independent prognostic factor of survival. The effect of c‐erbB‐2 expression seems to become more important in advanced stages of the disease. Since c‐erbB‐2 is a therapeutical target in other types of cancer, further studies to identify the role of c‐erbB‐2 in SCLC are clearly warranted. © 2001 Wiley‐Liss, Inc.