Background: Alterations in apoptosis-related proteins and DNA damage repair proteins are associated with resistance to chemotherapy or radiotherapy, which is the most important cause of treatment failure in small cell lung cancer (SCLC).
Patients and methods: Pretreatment tumor biopsy specimens from 77 patients with SCLC (limited stage: 40, extensive stage: 37) were analyzed for p53, bcl-2, bax and ERCC1 expression by immunohistochemistry. All patients were treated with platinum-based doublets. The most commonly used regimen was etoposide/cisplatin (50 patients). In patients with limited stage SCLC, thoracic irradiation was performed either concurrently with chemotherapy or sequentially.
Results: High expression of p53, bcl-2, bax and ERCC1 was observed in 40 (52%), 72 (94%), 38 (49%) and 13 (17%) patients, respectively. High expression of ERCC1 was associated with poor OS (1-year, 23% vs. 53%; p=0.026). When grouped according to stage, a significant correlation between high expression of ERCC1 and poor outcome was observed only in patients with limited stage SCLC (p=0.017). High expression of p53, bcl-2 and bax was not correlated with patient outcome. Multivariate analysis showed that extensive stage (p=0.006) and male gender (p=0.009) were independent predictors of poor OS, while high expression of ERCC1 failed to reach statistical significance despite a trend (p=0.057). In limited stage patients, high expression of ERCC1 was an independent prognostic factor for poor OS (p=0.046), along with male gender (p=0.033).
Conclusions: High expression of ERCC1 protein may be a useful predictor of poor outcome in SCLC patients treated with chemotherapy with or without radiotherapy, especially in limited stage SCLC.