Expression of ERCC1 and class III β-tubulin is associated with the survival of resected stage III non-small cell lung cancer patients treated with induction chemoradiotherapy using carboplatin-taxane

Huang,Cheng-Long; Kadota,Kyuichi; Liu,Dage; Ueno,Masaki; Nakasima,Nariyasu; Ishikawa,Shinya; Gotoh,Masashi; Misaki,Noriyuki; Chang,Sung-Soo; Yokomise,Hiroyasu

doi:10.3892/etm_00000069

Expression of ERCC1 and class III β-tubulin is associated with the survival of resected stage III non-small cell lung cancer patients treated with induction chemoradiotherapy using carboplatin-taxane

Authors:
- Cheng-Long Huang
- Kyuichi Kadota
- Dage Liu
- Masaki Ueno
- Nariyasu Nakasima
- Shinya Ishikawa
- Masashi Gotoh
- Noriyuki Misaki
- Sung-Soo Chang
- Hiroyasu Yokomise
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Affiliations: Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan. chuang@kms.ac.jp
Published online on: May 1, 2010 https://doi.org/10.3892/etm_00000069
Pages: 445-451

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Abstract

Several molecules have been proven to be associated with responsiveness to chemotherapy. A clinical study on the expression of excision repair cross-complementing (ERCC)-1 and class III β-tubulin was conducted in advanced stage non-small cell lung cancer (NSCLC) patients. We investigated 34 resected stage III NSCLC patients treated with induction chemoradiotherapy using carboplatin-taxane. Immunohistochemistry was performed to evaluate the intra-tumoral expression of ERCC1 and class III β-tubulin. Nineteen tumors (55.9%) were ERCC1-high and 11 (32.4%) were class III β-tubulin-high. There was no correlation between ERCC1 and class III β-tubulin expression (r=0.208). Regarding the pathological effect of induction therapy, the percentage of ERCC1-positive tumor cells was lower in tumors with a major response than in tumors with a minor response (P=0.0851). The percentage of class III β-tubulin-positive tumor cells was significantly lower in tumors with a major response than in tumors with a minor response (P=0.0105). Regarding patient survival, the overall survival was significantly higher in patients with ERCC1-low tumors than in those with ERCC1-high tumors (P=0.0034). The overall survival was also significantly higher in patients with class III β-tubulin-low tumors than in those with class III β-tubulin-high tumors (P=0.0185). Cox regression analysis also demonstrated that ERCC1 (P=0.0467) and class III β-tubulin statuses (P=0.0237) were significant prognostic factors. Co-evaluations of the intratumoral expression of ERCC1 and class III β-tubulin are clinically useful for identifying patient populations responsive to chemotherapy using carboplatin-taxane.

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1.	Arriagada R, Bergman B, Dunant A, et al: Cisplatin-based chemotherapy in patients with completely resected non-small cell lung cancer. N Engl J Med. 350:351–360. 2004. View Article : Google Scholar : PubMed/NCBI
2.	Winton T, Livingston R, Johnson D, et al: Vinorelbine plus cisplatin vs. observation in resected non-small cell lung cancer. N Engl J Med. 352:2589–2597. 2005. View Article : Google Scholar
3.	Hotta K, Matsuo K, Ueoka H, Kiura K, Tabata M and Tanimoto M: Role of adjuvant chemotherapy in patients with resected non-small cell lung cancer: reappraisal with a meta-analysis of randomized controlled trials. J Clin Oncol. 22:3860–3867. 2004. View Article : Google Scholar : PubMed/NCBI
4.	Huang C, Liu D, Masuya D, Nakashima T, Kameyama K, Ishikawa S, Ueno M, Haba R and Yokomise H: Clinical application of biological markers for treatments of resectable non-small cell lung cancers. Br J Cancer. 92:1231–1239. 2005. View Article : Google Scholar : PubMed/NCBI
5.	Bepler G: Using translational research to tailor the use of chemotherapy in the treatment of NSCLC. Lung Cancer. 50:S13–S14. 2005. View Article : Google Scholar : PubMed/NCBI
6.	Huang C, Yokomise H, Fukushima M and Kinoshita M: Tailor-made chemotherapy for non-small cell lung cancer patients. Future Oncol. 2:289–299. 2006. View Article : Google Scholar : PubMed/NCBI
7.	Mitsudomi T, Kosaka T, Endoh H, Horio Y, Hida T, Mori S, Hatooka S, Shinoda M, Takahashi T and Yatabe Y: Mutations of the epidermal growth factor receptor gene predict prolonged survival after gefitinib treatment in patients with non-small cell lung cancer with postoperative recurrence. J Clin Oncol. 23:2513–2520. 2005. View Article : Google Scholar
8.	Nakano J, Huang C, Liu D, Masuya D, Nakashima T, Yokomise H, Ueno M, Wada H and Fukushima M: Evaluations of biomarkers associated with 5-FU sensitivity for non-small cell lung cancer patients postoperatively treated with UFT. Br J Cancer. 95:607–615. 2006. View Article : Google Scholar : PubMed/NCBI
9.	Lord RV, Brabender J, Gandara D, et al: Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer. Clin Cancer Res. 8:2286–2291. 2002.PubMed/NCBI
10.	Olaussen KA, Dunant A, Fouret P, et al: DNA repair by ERCC1 in non-small cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med. 355:983–991. 2006. View Article : Google Scholar : PubMed/NCBI
11.	Metzger R, Leichman CG, Danenberg KD, et al: ERCC1 mRNA levels complement thymidylate synthase mRNA levels in predicting response and survival for gastric cancer patients receiving combination cisplatin and fluorouracil chemotherapy. J Clin Oncol. 16:309–316. 1998.
12.	Shirota Y, Stoehlmacher J, Brabender J, Xiong YP, Uetake H, Danenberg KD, Groshen S, Tsao-Wei DD, Danenberg PV and Lenz HJ: ERCC1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil chemotherapy. J Clin Oncol. 19:4298–4304. 2001.
13.	Seve P, Mackey J, Isaac S, Tredan O, Souquet PJ, Perol M, Lai R, Voloch A and Dumontet C: Class III β-tubulin expression in tumor cells predicts response and outcome in patients with non-small cell lung cancer receiving paclitaxel. Mol Cancer Ther. 4:2001–2007. 2005.
14.	Mozzetti S, Ferlini C, Concolino P, et al: Class III β-tubulin overexpression is a prominent mechanism of paclitaxel resistance in ovarian cancer patients. Clin Cancer Res. 11:298–305. 2005.
15.	Paradiso A, Mangia A, Chiriatti A, Tommasi S, Zito A, Latorre A, Schittulli F and Lorusso V: Biomarkers predictive for clinical efficacy of taxol-based chemotherapy in advanced breast cancer. Ann Oncol. 16(Suppl 4): 14–19. 2005. View Article : Google Scholar : PubMed/NCBI
16.	Yokomise H, Gotoh M, Okamoto T, Yamamoto Y, Ishikawa S, Nakashima T, Masuya D, Liu D and Huang CL: Induction chemoradiotherapy (carboplatin-taxane and concurrent 50-Gy radiation) for bulky cN2,N3 non-small cell lung cancer. J Thorac Cardiovasc Surg. 133:1179–1185. 2007. View Article : Google Scholar : PubMed/NCBI
17.	Therasse P, Arbuck SG, Eisenhauer EA, et al: New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 92:205–216. 2000. View Article : Google Scholar
18.	The Japanese Lung Cancer Society. Rule for Clinical and Pathological Record of Lung Cancer. 6th edition. Kanehara; Tokyo: pp. 168–169. 2003
19.	Rosell R, Taron M, Barnadas A, Scagliotti G, Sarries C and Roig B: Nucleotide excision repair pathways involved in cisplatin resistance in non-small cell lung cancer. Cancer Control. 10:297–305. 2003.PubMed/NCBI
20.	Rigas JR: Taxane-platinum combinations in advanced non-small cell lung cancer: a review. Oncologist. 9:16–23. 2004. View Article : Google Scholar : PubMed/NCBI
21.	Kelly K, Crowley J, Bunn PA Jr, et al: Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non-small cell lung cancer: a Southwest Oncology Group trial. J Clin Oncol. 19:3210–3218. 2001.PubMed/NCBI
22.	Burkhart CA, Kavallaris M and Horwitz SB: The role of β-tubulin isotypes in resistance to antimitotic drugs. Biochim Biophys Acta. 1471:1–9. 2001.
23.	Jordan MA and Wilson L: Microtubules as a target for anticancer drugs. Nat Rev Cancer. 4:253–265. 2004. View Article : Google Scholar : PubMed/NCBI
24.	Katsetos CD, Legido A, Perentes E and Mork SJ: Class III β-tubulin isotype: a key cytoskeletal protein at the crossroads of developmental neurobiology and tumor neuropathology. J Child Neurol. 18:851–866. 2003.
25.	Lu Q and Luduena RF: Removal of β-III isotype enhances taxol induced microtubule assembly. Cell Struct Funct. 18:173–182. 1993.
26.	Kamath K, Wilson L, Cabral F and Jordan MA: β III-tubulin induces paclitaxel resistance in association with reduced effects on microtubule dynamic instability. J Biol Chem. 280:12902–12907. 2005.
27.	Derry WB, Wilson L, Khan IA, Luduena RF and Jordan MA: Taxol differentially modulates the dynamics of microtubules assembled from unfractionated and purified β-tubulin isotypes. Biochemistry. 36:3554–3562. 1997.PubMed/NCBI
28.	Hari M, Yang H, Zeng C, Canizales M and Cabral F: Expression of class III β-tubulin reduces microtubule assembly and confers resistance to paclitaxel. Cell Motil Cytoskeleton. 56:45–56. 2003.
29.	Kavallaris M, Kuo DY, Burkhart CA, Regl DL, Norris MD, Haber M and Horwitz SB: Taxol-resistant epithelial ovarian tumors are associated with altered expression of specific β-tubulin isotypes. J Clin Invest. 100:1282–1293. 1997.PubMed/NCBI
30.	Ranganathan S, Benetatos CA, Colarusso PJ, Dexter DW and Hudes GR: Altered β-tubulin isotype expression in paclitaxel-resistant human prostate carcinoma cells. Br J Cancer. 77:562–566. 1998.