Abstract
Excision Repair Cross-Complementing Group 1 (ERCC1) is an important DNA repair gene, playing critical role in nucleotide excision repair pathway and having a significant influence on genomic instability. Some studies support that ERCC1 might be a potential predictive and prognostic marker in non-small cell lung cancer (NSCLC). ERCC1 has also been shown to be a promising biomarker in NSCLC treated with a cisplatin-based regimen. Therefore, the determination of ERCC1 expression at DNA, mRNA and protein level in different stages of NSCLC is still an important topic in the cancer. Ninety-one formalin-fixed paraffin-embedded tumor samples histopathologically diagnosed as NSCLC were examined in this study. ERCC1 expression at protein level were scored by immunohistochemistry. The gene amplification and mRNA expression levels for ERCC1 were determined by real-time quantitative PCR. There was complete concordance among the three methods in 39 tumor samples (42.9%). A strong correlation was found between DNA amplification and mRNA expression (r = 0.662) while there was no correlation between mRNA and protein assessment for ERCC1 expression (r = −0.013). ERCC1 expression at mRNA and DNA level (63.1 and 84.2%, respectively) in tumors at stage III was higher than at the other stages. In contrast, the protein expression at stage II and III (56.6 and 52.6%, respectively) of NSCLC was lower than that of tumors with stage I NSCLC. These results show that the mechanism by which ERCC1 expression might play a role in tumor behavior. This study was also confirmed that the appropriate validation and qualification in methods used for ERCC1 status were needed before its clinical application and implementation.
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References
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ (2008) Cancer Statistics, 2008. CA Cancer J Clin 58(2):71–96
Ministry of Health Republic of Turkey (2009) Cancer statistics in Turkey. http://www.kanser.gov.tr. Accessed Dec 2010
Simon GR, Sharma A, Cantor A, Smith P, Bepler G (2005) ERCC1 expression is a predictor of survival in resected patients with non-small cell lung cancer. Chest 127(3):978–983
Lord RV, Brabender J, Gandara D et al (2002) Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer. Clin Cancer Res 8:2286–2291
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(10):983–991
Fujii T, Toyooka S, Ichimura K et al (2008) ERCC1 protein expression predicts the response of cisplatin-based neoadjuvant chemotherapy in non-small-cell lung cancer. Lung Cancer 59(3):377–384
De Silva IU, McHugh PJ, Clingen PH, Hartley JA (2000) Defining the roles of nucleotide excision repair and recombination in the repair of DNA interstrand cross-links in mammalian cells. Mol Cell Biol 20:7980–7990
Reed E (1998) Platinum-DNA adduct, nucleotide excision repair and platinum based anti-cancer chemotherapy. Cancer Treat Rev 24:331–344
Niedernhofer LJ, Odijk H, Budzowska M et al (2004) The structure-specific endonuclease Ercc1-Xpf is required to resolve DNA interstrand cross-link-induced double-strand breaks. Mol Cell Biol 24(13):5776–5787
Li J, Li ZN, Du YJ, Li XQ, Bao QL, Chen P (2009) Expression of MRP1, BCRP, LRP, and ERCC1in advanced non-small-cell lung cancer: correlation with response to chemotherapy and survival. Clin Lung Cancer 10(6):414–421
Scheil-Bertram S, Tylus-Schaaf P, du Bois A, Harter P, Oppitz M, Ewald-Riegler N, Fisseler-Eckhoff A (2010) Excision repair cross-complementation group 1 protein overexpression as a predictor of poor survival for high-grade serous ovarian adenocarcinoma. Gynecol Oncol 119(2):325–331
Ceppi P, Papotti M, Scagliotti G (2010) New strategies for targeting the therapy of NSCLC: the role of ERCC1 and TS. Adv Med Sci 55(1):22–25
Vilmar A, Santoni-Rugiu E, Sørensen JB (2010) ERCC1, toxicity and quality of life in advanced NSCLC patients randomized in a large multicentre phase III trial. Eur J Cancer 46:1554–1562
Cobo M, Isla D, Massuti B et al (2007) Customizing cisplatin based on quantitative excision repair cross-complementing 1 mRNA expression: a phase III trial in non-small-cell lung cancer. J Clin Oncol 25(19):2747–2754
Olaussen KA, Mountzios G, Soria JC (2007) ERCC1 as a risk stratifier in platinum-based chemotherapy for nonsmall-cell lung cancer. Curr Opin Pulm Med 13(4):284–289
Ren S, Zhou S, Zhang L et al (2010) High-level mRNA of excision repair cross-complementation group 1 gene is associated with poor outcome of platinum-based doublet chemotherapy of advanced nonsmall cell lung cancer patients. Cancer Invest 28(10):1078–1083
Booton R, Ward T, Ashcroft L, Morris J, Heighway J, Thatcher N (2007) ERCC1 mRNA expression is not associated with response and survival after platinum-based chemotherapy regimens in advanced non-small cell lung cancer. J Thorac Oncol 2(10):902–906
Travis WD, Brambilla E, Müller-Hermelink HK, Haris CC (2004) Tumours of the lung. In: World Health Organization classification of tumours: pathology & genetics—tumours of lung, pleura, thymus, and heart. IARC Press, Lyon, pp 10–11
Lee KH, Min HS, Han SW et al (2008) ERCC1 expression by immunohistochemistry and EGFR mutations in resected non-small cell lung cancer. Lung Cancer 60(3):401–407
Ceppi P, Volante M, Novello S et al (2006) ERCC1 and RRM1 gene expressions but not EGFR are predictive of shorter survival in advanced non-small-cell lung cancer treated with cisplatin and gemcitabine. Ann Oncol 17(12):1818–1825
Takenaka T, Yano T, Kiyohara C et al (2009) Effects of excision repair cross-complementation group 1 (ERCC1) single nücleotide polymorphisms on the prognosis of non-small cell lung cancer patients. Lung Cancer 67(1):101–107
Smith S, Su D, Longrais IA et al (2007) ERCC1 genotype and phenotype in epithelial ovarian cancer ıdentify patients likely to benefit from paclitaxel treatment in addition to platinum-based therapy. J Clin Oncol 25:5172–5179
Wang L, Aakre JA, Jiang R et al (2010) Methylation markers for small cell lung cancer in peripheral blood leukocyte DNA. J Thorac Oncol 5(6):778–785
Azuma K, Komohara Y, Sasada T et al (2007) Excision repair cross-complementation group 1 predicts progression-free and overall survival in non-small cell lung cancer patients treated with platinum-based chemotherapy. Cancer Sci 98(9):1336–1343
Yu JJ, Mu C, Lee KB (2006) A nucleotide polymorphism in ERCC1 in human ovarian cancer cell lines and tumor tissues. Mutat Res 382:13–20
Zhou W, Liu G, Park S et al (2005) Gene smoking ınteraction associations for the ERCC1 polymorphisms in the risk of lung cancer. Cancer Epidemiol Biomarkers Prev 14:491–496
Britten RA, Liu D, Tessier A, Hutchison MJ, Murray D (2000) ERCC1 expression as a molecular marker of cisplatin resistance in human cervical tumor cells. Int J Cancer 89(5):453–457
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
Simon G, Sharma A, Li X (2007) Feasibility and efficacy of molecular analysis-directed individualized therapy in advanced non-small-cell lung cancer. J Clin Oncol 25(19):2741–2746
Chang IY, Kim MH, Kim HB, Lee DY, Kim SH, Kim HY, You HJ (2005) Small interfering RNA-induced suppression of ERCC1 enhances sensitivity of human cancer cells to cisplatin. Biochem Biophys Res Commun 327(1):225–233
Lan L, Hayashi T, Rabeya RM et al (2004) Functional and physical interactions between ERCC1 and MSH2 complexes for resistance to cis-diamminedichloroplatinum(II) in mammalian cells. DNA Repair 3(2):135–143
Niedernhofer LJ, Bhagwat N, Wood RD (2007) ERCC1 and non-small-cell lung cancer. N Engl J Med 356(24):2538–2540
Reed E (2005) ERCC1 and clinical resistance to platinum-based therapy. Clin Cancer Res 11(17):6100–6102
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The authors wish to acknowledge the financial support provided by a grant from The Scientific and Technological Research Council of Turkey, TUBITAK (Grant No. 109S022).
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Tepeli, E., Caner, V., Büyükpınarbaşılı, N. et al. Expression of ERCC1 and its clinicopathological correlations in non-small cell lung cancer. Mol Biol Rep 39, 335–341 (2012). https://doi.org/10.1007/s11033-011-0743-0
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DOI: https://doi.org/10.1007/s11033-011-0743-0