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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 proportionalhazard 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. Key words: small-cell lung cancer; c-erbB-2; HER-2/neu; prognosisLung cancer is the leading cause of cancer-related death in western industrial countries. Small-cell lung cancer (SCLC) represents 15% to 25% of all lung cancer types and is distinguished from non-small-cell lung cancer (NSCLC) by histology alone. Important clinical differences are rapid tumor doubling time, high growth fraction and early development of widespread metastases. 1 While SCLC is considered highly responsive to initial chemotherapy or radiotherapy, relapse despite treatment occurs within 2 years. 2,3 Only 10% of patients survive longer than 2 years after institution of therapy. Five-year survival rate ranges only from 3% to 7%. 4,5 It is hoped that progress toward understanding the molecular biology of SCLC will provide new therapeutic strategies and will benefit patients suffering f...

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