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Decreased ERCC1 Expression After Platinum-Based Neoadjuvant Chemotherapy in non-Small Cell Lung Cancer

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Pathology & Oncology Research

Abstract

We have already demonstrated in a small cohort of 17 non-small cell lung cancer patients that ERCC1 (excision repair cross-complementation group 1) protein expression decreased after platinum-based treatment, however, certain clinicopathological parameters, such as histologic subtypes, ERCC1 expression scores, chemotherapeutic combinations, response rate, gender and smoking history were not analyzed. The aim of our present study was to extend the studied cohort and analyze those parameters. ERCC1 protein expression was examined in 46 patients treated with neoadjuvant chemotherapy. 46 bronchoscopic biopsy samples (27 squamous cell carcinomas /SCC/ and 19 adenocarcinomas /ADC/) together with their corresponding surgical biopsies were studied. ERCC1 immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissues. Staining scores were calculated by multiplying the percentage of positive tumor cells (0–100) by the staining intensity (0–3). 24/27 bronchoscopic SCC tissues expressed ERCC1. Thirteen of these cases became negative after neoadjuvant therapy and the expression differences between pre- and postchemotherapy samples were highly significant (p < 0.001). 11/19 bronchoscopic ADC tissues expressed ERCC1. Six of these cases became negative after neoadjuvant therapy and the expression differences were significant (p < 0.010). There was no newly expressed ERCC1 postoperatively. Comparison of staining score changes revealed more pronounced decrease in SCC (p = 0.032). We observed no correlation between initial ERCC1 level or ERCC1 decrease and overall survival, but we demonstrated correlations between decrease in ERCC1 expression and histologic subtypes of tumors and gender. We could confirm our previous data in a larger cohort that platinum-based chemotherapy affects the ERCC1 expression probably referring to an induction of tumor cell selection.

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Abbreviations

ERCC1:

excision repair cross-complementation group 1

NSCLC:

non-small cell lung cancer

ADC:

adenocarcinoma

SCC:

squamous cell carcinoma

References

  1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127(12):2893–2917. doi:10.1002/ijc.25516

    Article  CAS  PubMed  Google Scholar 

  2. Carbone DP, Felip E (2011) Adjuvant therapy in non-small cell lung cancer: future treatment prospects and paradigms. Clin Lung Cancer 12(5):261–271. doi:10.1016/j.cllc.2011.06.002

    Article  CAS  PubMed  Google Scholar 

  3. Le Chevalier T (2010) Adjuvant chemotherapy for resectable non-small-cell lung cancer: where is it going? Ann Oncol 21(7):196–-198. doi:10.1093/annonc/mdq376

    Google Scholar 

  4. Song WA, Zhou NK, Wang W, Chu XY, Liang CY, Tian XD, Guo JT, Liu X, Liu Y, Dai WM (2010) Survival benefit of neoadjuvant chemotherapy in non-small cell lung cancer: an updated meta-analysis of 13 randomized control trials. J Thorac Oncol 5(4):510–516. doi:10.1097/JTO.0b013e3181cd3345

    Article  PubMed  Google Scholar 

  5. Mouillet G, Monnet E, Milleron B, Puyraveau M, Quoix E, David P, Ducolone A, Molinier O, Zalcman G, Depierre A, Westeel V (2012) Pathologic complete response to preoperative chemotherapy predicts cure in early-stage non-small-cell lung cancer: combined analysis of two IFCT randomized trials. J Thorac Oncol 7(5):841–849. doi:10.1097/JTO.0b013e31824c7d92

    Article  CAS  PubMed  Google Scholar 

  6. Zheng Z, Chen T, Li X, Haura E, Sharma A, Bepler G (2007) DNA synthesis and repair genes RRM1 and ERCC1 in lung cancer. N Engl J Med 356(8):800–808. doi:10.1056/NEJMoa065411

    Article  CAS  PubMed  Google Scholar 

  7. Kang CH, Jang BG, Kim DW, Chung DH, Kim YT, Jheon S, Sung SW, Kim JH (2010) The prognostic significance of ERCC1, BRCA1, XRCC1, and betaIII-tubulin expression in patients with non-small cell lung cancer treated by platinum- and taxane-based neoadjuvant chemotherapy and surgical resection. Lung Cancer 68(3):478–483. doi:10.1016/j.lungcan.2009.07.004

    Article  PubMed  Google Scholar 

  8. Soria JC (2007) ERCC1-tailored chemotherapy in lung cancer: the first prospective randomized trial. J Clin Oncol 25(19):2648–2649. doi:10.1200/jco.2007.11.3167

    Article  CAS  PubMed  Google Scholar 

  9. Papay J, Sapi Z, Egri G, Gyulai M, Szende B, Losonczy G, Timar J, Moldvay J (2009) Platinum-based chemotherapy in lung cancer affects the expression of certain biomarkers including ERCC1. Pathol Oncol Res 15(3):445–450. doi:10.1007/s12253-009-9155-z

    Article  CAS  PubMed  Google Scholar 

  10. Rami-Porta R, Crowley JJ, Goldstraw P (2009) The revised TNM staging system for lung cancer. Ann Thorac Cardiovasc Surg 15(1):4–9

    PubMed  Google Scholar 

  11. Kerr KM (2012) Personalized medicine for lung cancer: new challenges for pathology. Histopathology 60(4):531–546. doi:10.1111/j.1365-2559.2011.03854.x

    Article  PubMed  Google Scholar 

  12. Pomerri F, Pucciarelli S, Gennaro G, Maretto I, Nitti D, Muzzio PC (2012) Comparison between CT volume measurement and histopathological assessment of response to neoadjuvant therapy in rectal cancer. Eur J Radiol 81(12):3918–3924. doi:10.1016/j.ejrad.2012.04.038

    Article  PubMed  Google Scholar 

  13. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247. doi:10.1016/j.ejca.2008.10.026

    Article  CAS  PubMed  Google Scholar 

  14. Nishino M, Jackman DM, Hatabu H, Yeap BY, Cioffredi LA, Yap JT, Janne PA, Johnson BE, Van den Abbeele AD (2010) New response evaluation criteria in solid tumors (RECIST) guidelines for advanced non-small cell lung cancer: comparison with original RECIST and impact on assessment of tumor response to targeted therapy. AJR Am J Roentgenol 195(3):W221–228. doi:10.2214/ajr.09.3928

    Article  PubMed Central  PubMed  Google Scholar 

  15. Lee HY, Lee KS, Ahn MJ, Hwang HS, Lee JW, Park K, Ahn JS, Kim TS, Yi CA, Chung MJ (2011) New CT response criteria in non-small cell lung cancer: proposal and application in EGFR tyrosine kinase inhibitor therapy. Lung Cancer 73(1):63–69. doi:10.1016/j.lungcan.2010.10.019

    Article  PubMed  Google Scholar 

  16. Burger IA, Schwarz EI, Samarin A, Breitenstein S, Weber A, Hany TF (2013) Correlation between therapy response assessment using FDG PET/CT and histopathologic tumor regression grade in hepatic metastasis of colorectal carcinoma after neoadjuvant therapy. Ann Nucl Med 27(2):177–183. doi:10.1007/s12149-012-0670-8

    Article  CAS  PubMed  Google Scholar 

  17. Pataer A, Kalhor N, Correa AM, Raso MG, Erasmus JJ, Kim ES, Behrens C, Lee JJ, Roth JA, Stewart DJ, Vaporciyan AA, Wistuba II, Swisher SG (2012) Histopathologic response criteria predict survival of patients with resected lung cancer after neoadjuvant chemotherapy. J Thorac Oncol 7(5):825–832. doi:10.1097/JTO.0b013e318247504a

    Article  PubMed Central  PubMed  Google Scholar 

  18. Sun Y, Campisi J, Higano C, Beer TM, Porter P, Coleman I, True L, Nelson PS (2012) Treatment-induced damage to the tumor microenvironment promotes prostate cancer therapy resistance through WNT16B. Nat Med 18(9):1359–1368. doi:10.1038/nm.2890

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Xiang F, Yu W, Shen Y, Wu C, Wang Y (2007) Effects of neoadjuvant chemotherapy on the quantitative expression of P-gp, LRP, MRP, GST-pi in NSCLC and its clinical significance. Zhongguo Fei Ai Za Zhi 10(5):398–405. doi:10.3779/j.issn.1009-3419.2007.05.11

    CAS  PubMed  Google Scholar 

  20. Liu YP, Yang CJ, Huang MS, Yeh CT, Wu AT, Lee YC, Lai TC, Lee CH, Hsiao YW, Lu J, Shen CN, Lu PJ, Hsiao M (2013) Cisplatin selects for multidrug-resistant CD133+ cells in lung adenocarcinoma by activating Notch signaling. Cancer Res 73(1):406–416. doi:10.1158/0008-5472.can-12-1733

    Article  CAS  PubMed  Google Scholar 

  21. Meert AP, Martin B, Verdebout JM, Paesmans M, Berghmans T, Ninane V, Sculier JP (2004) Correlation of different markers (p53, EGF-R, c-erbB-2, Ki-67) expression in the diagnostic biopsies and the corresponding resected tumors in non-small cell lung cancer. Lung Cancer 44(3):295–301. doi:10.1016/j.lungcan.2003.12.009

    Article  PubMed  Google Scholar 

  22. Choi CM, Yang SC, Jo HJ, Song SY, Jeon YJ, Jang TW, Kim DJ, Jang SH, Yang SH, Kim YD, Lee KH, Jang SJ, Kim YT, Kim DK, Chung DH, Kim L, Nam HS, Cho JH, Kim HJ, Ryu JS (2012) Proteins involved in DNA damage response pathways and survival of stage I non-small-cell lung cancer patients. Ann Oncol 23(8):2088–2093. doi:10.1093/annonc/mdr606

    Article  CAS  PubMed  Google Scholar 

  23. Kang CH, Jang BG, Kim DW, Chung DH, Kim YT, Jheon S, Sung SW, Kim JH (2009) Differences in the expression profiles of excision repair cross complementation group 1, x-ray repair cross complementation group 1, and betaIII-tubulin between primary non-small cell lung cancer and metastatic lymph nodes and the significance in mid-term survival. J Thorac Oncol 4(11):1307–1312. doi:10.1097/JTO.0b013e3181b9f236

    Article  PubMed  Google Scholar 

  24. Schneider S, Uchida K, Brabender J, Baldus SE, Yochim J, Danenberg KD, Salonga D, Chen P, Tsao-Wei D, Groshen S, Hoelscher AH, Schneider PM, Danenberg PV (2005) Down regulation of TS, DPD, ERCC1, GST-Pi, EGFR, and HER2 gene expression after neoadjuvant three-modality treatment in patients with esophageal cancer. J Am Coll Surg 200(3):336–344. doi:10.1016/j.jamcollsurg.2004.10.035

    Article  PubMed  Google Scholar 

  25. Xia Y, Hu C, Zhang M, Yang H, Zhou D, Liang S (2007) Relationship between ERCC1 expression and cisplatin intervention in human lung adenocarcinoma cell lines. Zhongguo Fei Ai Za Zhi 10(5):362–365. doi:10.3779/j.issn.1009-3419.2007.05.03

    CAS  PubMed  Google Scholar 

  26. Baba H, Watanabe M, Okabe H, Miyamoto Y, Sakamoto Y, Baba Y, Iwatsuki M, Chikamoto A, Beppu T (2012) Up regulation of ERCC1 and DPD expressions after oxaliplatin-based first-line chemotherapy for metastatic colorectal cancer. Br J Cancer 107(12):1950–1955. doi:10.1038/bjc.2012.502

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Olaussen KA, Dunant A, Fouret P, Brambilla E, Andre F, Haddad V, Taranchon E, Filipits M, Pirker R, Popper HH, Stahel R, Sabatier L, Pignon JP, Tursz T, Le Chevalier T, Soria JC (2006) DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med 355(10):983–91

    Article  CAS  PubMed  Google Scholar 

  28. Schneider JG1, Farhadfar N, Sivapiragasam A, et al. Commercial Laboratory Testing of Excision Repair Cross-Complementation Group 1 Expression in Non-Small Cell Lung Cancer. Oncologist. 2014 Apr 4. [Epub ahead of print]

  29. Pierceall WE, Olaussen KA, Rousseau V, Brambilla E, Sprott KM, Andre F, Pignon JP, Le Chevalier T, Pirker R, Jiang C, Filipits M, Chen Y, Kutok JL, Weaver DT, Ward BE, Soria JC (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(9):2245–52. doi:10.1093/annonc/mdr624

    Article  CAS  PubMed  Google Scholar 

  30. Olaussen KA, Adam J, Vanhecke E, Vielh P, Pirker R, Friboulet L, Popper H, Robin A, Commo F, Thomale J, Kayitalire L, Filipits M, Le Chevalier T, Andre F, Brambilla E, Soria JC (2013) PARP1 impact on DNA repair of platinum adducts: preclinical and clinical read-outs. Lung Cancer 80(2):216–22. doi:10.1016/j.lungcan.2013.01.014

    Article  PubMed  Google Scholar 

  31. Yoon YK, Im SA, Min A, Kim HP, Hur HS, Lee KH, Han SW, Song SH, Youn Oh D, Kim TY, Kim WH, Bang YJ (2012) Sunitinib synergizes the antitumor effect of cisplatin via modulation of ERCC1 expression in models of gastric cancer. Cancer Lett 321(2):128–136. doi:10.1016/j.canlet.2012.01.019

    Article  CAS  PubMed  Google Scholar 

  32. Guarneri V, Dieci MV, Barbieri E, Piacentini F, Omarini C, Ficarra G, Bettelli S, Conte PF (2013) Loss of HER2 positivity and prognosis after neoadjuvant therapy in HER2-positive breast cancer patients. Ann Oncol. doi:10.1093/annonc/mdt364

    Google Scholar 

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Acknowledgments

The authors thank Mrs. Anna Tamási for her excellent technical assistance and Mrs. Elvira Kálé for correcting the manuscript.

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Correspondence to Katalin Fábián.

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Podmaniczky, E., Fábián, K., Pápay, J. et al. Decreased ERCC1 Expression After Platinum-Based Neoadjuvant Chemotherapy in non-Small Cell Lung Cancer. Pathol. Oncol. Res. 21, 423–431 (2015). https://doi.org/10.1007/s12253-014-9839-x

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