Expression of ERCC1, MSH2 and PARP1 in Non-small Cell Lung Cancer and Prognostic Value in Patients Treated with Platinum-based Chemotherapy

  • Xie, Ke-Jie ;
  • He, Hong-Er ;
  • Sun, Ai-Jing ;
  • Liu, Xi-Bo ;
  • Sun, Li-Ping ;
  • Dong, Xue-Jun
  • Published : 2014.03.30


Purpose: To evaluate the prognostic value of the expression of excision repair cross-complementation group l (ERCC1), MutS protein homolog 2 (MSH2) and poly ADP-ribose polymerase 1 (PARP1) in non-small-cell lung cancer patients receiving platinum-based postoperative adjuvant chemotherapy. Methods: Immunohistochemistry was applied to detect the expression of ERCC1, MSH2 and PARP1 in 111 cases of non-small cell lung cancer paraffin embedded surgical specimens. Through og-rank survival analysis, we evaluated the prognostic value of the ERCC1, MSH2, PARP1 and the related clinicopathological factors. COX regression analysis was used to determine whether ERCC1, MSH2 and PARP1 were independent prognostic factors. Results: In the enrolled 111 non-small cell lung cancer patients, the positive expression rate of ERCC1, MSH2 and RARP1 was 33.3%, 36.9% and 55.9%, respectively. ERCC1 (P<0.001) and PARP1 (P=0.033) were found to be correlated with the survival time while there was no correlation for MSH2 (P=0.298). Patients with both ERCC1 and PARP1 negative cancer had significantly longer survival time than those with ERCC1 (P=0.042) or PARP1 (P=0.027) positive alone. Similalry, the survival time of patients with both ERCC1 and PARP1 positive cancer was shorter than those with ERCC1 (P=0.048) or PARP1 (P=0.01) positive alone. Conclusion: Patients with ERCC1 or PARP1 negative non-small cell lung cancer appear to benefit from platinum-based postoperative adjuvant chemotherapy.


DNA repair gene;ERCC1;MSH2;RARP1;non-small cell lung cancer;prognosis;chemotherapy


  1. Olaussen K A, Adam J, Vanhecke E, et al (2013). PARP1 impact on DNA repair of platinum adducts: preclinical and clinical read-outs. Lung Cancer, 80, 216-22.
  2. Kummar S, Chen A, Parchment RE, et al (2012). Advances in using PARP inhibitors to treat cancer. BMC medicine, 10, 25.
  3. Li X-D, Han J-C, Zhang Y-J, et al (2013). Common variations of DNA repair genes are associated with response to platinumbased chemotherapy in NSCLCs. Asian Pac J Cancer Prev, 14, 145-8.
  4. Michels J, Vitale I, Galluzzi L, et al (2013). Cisplatin resistance associated with PARP hyperactivation. Cancer Res, 73, 2271-80.
  5. Olaussen KA, Dunant A, Fouret P, et al (2006). DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med, 355, 983-91.
  6. Ozdemir O, Ozdemir P, Veral A, et al (2013). ERCC1 expression does not predict survival and treatment response in advanced stage non-small cell lung cancer cases treated with platinum based chemotherapy. Asian Pac J Cancer Prev, 14, 4679-83.
  7. Parkin DM, Bray F, Ferlay J, Pisani P (2005). Global cancer statistics, 2002. CA Cancer J Clin, 55, 74-108.
  8. Parsons JL, Dianova, II, Allinson SL, Dianov GL (2005). Poly(ADP-ribose) polymerase-1 protects excessive DNA strand breaks from deterioration during repair in human cell extracts. FEBS J, 272, 2012-21.
  9. Pierceall WE, Olaussen KA, Rousseau V, et al (2012). Cisplatin benefit is predicted by immunohistochemical analysis of DNA repair proteins in squamous cell carcinoma but not adenocarcinoma: theranostic modeling by NSCLC constituent histological subclasses. Ann Oncol, 23, 2245-52.
  10. Arriagada R, Bergman B, Dunant A, et al (2004). Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med, 350, 351-60.
  11. Bahl A, Falk S (2001). Meta-analysis of single agents in the chemotherapy of NSCLC: what do we want to know? Br J Cancer, 84, 1143-5.
  12. Friboulet L, Olaussen KA, Pignon JP, et al (2013). ERCC1 isoform expression and DNA repair in non-small-cell lung cancer. N Engl J Med, 368, 1101-10.
  13. Friedberg EC (2001). How nucleotide excision repair protects against cancer. Nature reviews. Cancer, 1, 22-33.
  14. Hays JB, Hoffman PD, Wang H (2005). Discrimination and versatility in mismatch repair. DNA repair, 4, 1463-74.
  15. Jassem J, Skokowski J, Dziadziuszko R, et al (2000). Results of surgical treatment of non-small cell lung cancer: validation of the new postoperative pathologic TNM classification. J Thorac Cardiovasc Surg, 119, 1141-6.
  16. Jemal A, Murray T, Ward E, et al (2005). Cancer statistics, 2005. CA Cancer J Clin, 55, 10-30.
  17. Jemal A, Siegel R, Ward E, et al (2006). Cancer statistics, 2006. CA Cancer J Clin, 56, 106-30.
  18. Kamal NS, Soria JC, Mendiboure J, et al (2010). MutS homologue 2 and the long-term benefit of adjuvant chemotherapy in lung cancer. Clin Cancer Res, 16, 1206-15.
  19. Roth JA, Carlson JJ (2011). Prognostic role of ERCC1 in advanced non-small-cell lung cancer: a systematic review and meta-analysis. Clin Lung Cancer, 12, 393-401.
  20. Pignon JP, Tribodet H, Scagliotti GV, et al (2008). Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol, 26, 3552-9.
  21. Rosell R, Lord RV, Taron M, Reguart N (2002). DNA repair and cisplatin resistance in non-small-cell lung cancer. Lung cancer, 38, 217-27.
  22. Rosell R, Skrzypski M, Jassem E, et al (2007). BRCA1: a novel prognostic factor in resected non-small-cell lung cancer. PloS one, 2, e1129.
  23. Rouleau M, Patel A, Hendzel MJ, et al (2010). PARP inhibition: PARP1 and beyond. Nat Rev Cancer, 10, 293-301.
  24. Scartozzi M, Franciosi V, Campanini N, et al (2006). Mismatch repair system (MMR) status correlates with response and survival in non-small cell lung cancer (NSCLC) patients. Lung Cancer, 53, 103-9.
  25. Vageli DP, Zaravinos A, Daniil Z, et al (2012). hMSH2 and hMLH1 gene expression patterns differ between lung adenocarcinoma and squamous cell carcinoma: correlation with patient survival and response to adjuvant chemotherapy treatment. Int J Biol Markers, 27, e400-4.
  26. Wang D, Xiang DB, Yang XQ, et al (2009). APE1 overexpression is associated with cisplatin resistance in non-small cell lung cancer and targeted inhibition of APE1 enhances the activity of cisplatin in A549 cells. Lung Cancer, 66, 298-304.
  27. Zhang Z-Y, Tian X, Wu R, et al (2012). Predictive role of ERCC1 and XPD genetic polymorphisms in survival of Chinese non-small cell lung cancer patients receiving chemotherapy. Asian Pac J Cancer Prev, 13, 2583-6.

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