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Expression of excision repair cross-complementation group 1 protein predicts poor outcome in patients with small cell
Hyun Woo Lee1, Jae Ho Han, Jang Hee Kim
1Department of Hematology-Oncology, Ajou University School of Medicine, Suwon 443-721, Republic of Korea.
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.
Insights
High expression of ERCC1 protein may predict poor outcomes in small cell lung cancer (SCLC) patients undergoing chemotherapy or radiotherapy. This finding is particularly relevant for limited-stage SCLC, highlighting ERCC1 as a potential prognostic marker.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Treatment failure in small cell lung cancer (SCLC) is often linked to resistance to chemotherapy or radiotherapy.
- This resistance is associated with alterations in apoptosis-related and DNA damage repair proteins.
Purpose of the Study:
- To investigate the association between the expression of p53, bcl-2, bax, and ERCC1 proteins and patient outcomes in small cell lung cancer (SCLC).
- To determine the prognostic value of these proteins in SCLC patients treated with platinum-based chemotherapy, with or without radiotherapy.
Main Methods:
- Immunohistochemistry was used to analyze pretreatment tumor biopsy specimens from 77 SCLC patients.
- Expression levels of p53, bcl-2, bax, and ERCC1 were assessed.
- Patients received platinum-based doublet chemotherapy, with thoracic irradiation for limited-stage SCLC.
Main Results:
- High ERCC1 expression was observed in 17% of patients and was significantly associated with poorer overall survival (OS), especially in limited-stage SCLC.
- High expression of p53, bcl-2, and bax did not correlate with patient outcomes.
- Multivariate analysis identified extensive stage and male gender as independent predictors of poor OS, while ERCC1 showed a trend.
Conclusions:
- High ERCC1 protein expression may serve as a useful predictor of poor outcomes in SCLC patients.
- This predictive value is particularly noted in limited-stage SCLC patients receiving chemotherapy with or without radiotherapy.