International Journal of Clinical Oncology

, Volume 18, Issue 3, pp 371–379

The role of βIII-tubulin in non-small cell lung cancer patients treated by taxane-based chemotherapy

  • Kyoichi Kaira
  • Toshiaki Takahashi
  • Haruyasu Murakami
  • Takehito Shukuya
  • Hirotsugu Kenmotsu
  • Akira Ono
  • Tateaki Naito
  • Asuka Tsuya
  • Yukiko Nakamura
  • Masahiro Endo
  • Haruhiko Kondo
  • Takashi Nakajima
  • Nobuyuki Yamamoto
Original Article

Abstract

Background

The aim of this study is to evaluate whether class III β-tubulin (TUBB3) expression could predict progression-free survival or overall survival in relapsed non-small cell lung cancer (NSCLC) patients treated with taxene-based chemotherapy.

Methods

Immunohistochemistal staining was used to examine the expression of TUBB3 in resected lung tumor specimens obtained from 56 patients treated with platinum-based chemotherapy against recurrent tumors after curative resections. Excision repair cross-complementation group 1, breast cancer susceptibility gene 1, vascular endothelial growth factor, Ki-67, CD34, and p53 were also correlated with clinical features and outcome after treatment.

Results

Of the 56 patients enrolled in the study, 29 were treated by carboplatin plus paclitaxel as first-line treatment, and 24 patients received docetaxel monotherapy as second- or third-line treatment. A positive TUBB3 expression is closely associated with a poor response to taxane-based chemotherapy. TUBB3 expression was an independent prognostic factor for predicting poor progression-free survival after docetaxel administration. However, TUBB3 expression could not predict outcome after carboplatin plus paclitaxel treatment. The other biomarkers tested were not independent prognostic factors for predicting outcome after taxane-based chemotherapy.

Conclusion

TUBB3 expression is associated with resistance to taxane-based chemotherapy and is an independent prognostic factor for predicting poor progression-free survival after docetaxel treatment alone. TUBB3 expression may be a predictive marker for chemoresistance to docetaxel in NSCLC with postoperative recurrent disease.

Keywords

Class III β-tubulin Taxane Chemotherapy NSCLC Chemoresistance Prognosis 

References

  1. 1.
    Kawaguchi T, Takada M, Kubo A et al (2010) Performance status and smoking status are independent favorable prognostic factors for survival in non-small cell lung cancer. A comprehensive analysis of 26,957 patients with NSCLC. J Thorac Oncol 5:620–630PubMedGoogle Scholar
  2. 2.
    Kaira K, Yamamoto N (2010) Prognostic and predictive factors in resected non-small cell lung cancer. Expert Opin Med Diagn 4:1–9CrossRefGoogle Scholar
  3. 3.
    Jordan MA, Wilson L (2001) Microtubules as a target for anticancer drugs. Nat Rev Cancer 4:253–265CrossRefGoogle Scholar
  4. 4.
    Kang CH, Jang BG, Kim DW et al (2010) The prognostic significance of ERCC1, XRCC1, and β III-tubulin expression in patients with non-small cell lung cancer treated by platinum- and taxane-based neoadjuvant chemotherapy and surgical resection. Lung Cancer 68:478–483PubMedCrossRefGoogle Scholar
  5. 5.
    Seve P, Reiman T, Dumontet C (2010) The role of βIII-tubulin in predicting chemoresistance in non-small cell lung cancer. Lung Cancer 67:136–143Google Scholar
  6. 6.
    Azuma K, Sasada K, Kawahara A et al (2009) Expression of ERCC1 and class III β-tubulin in non-small cell lung cancer patients treated with carboplatin and paclitaxel. Lung Cancer 64:326–333PubMedCrossRefGoogle Scholar
  7. 7.
    Rosell R, Scagliotti G, Danenberg KD et al (2003) Transcripts in pretreatment biopsies from a three-arm randomized trial in metastatic non-small cell lung cancer. Oncogene 22:3548–3552PubMedCrossRefGoogle Scholar
  8. 8.
    Dumontet C, Isaac S, Souquet PJ et al (2005) Expression of class III beta tubulin in non-small cell lung cancer is correlated with resistance to taxane chemotherapy. Bull Cancer 92:E25–E30PubMedGoogle Scholar
  9. 9.
    Seve P, Issac S, Tredan O et al (2005) Expression of class III β-tubulin is predictive of patient outcome in patients with non-small cell lung cancer receiving vinorelbine-based chemotherapy. Clin Cancer Res 11:5481–5486PubMedCrossRefGoogle Scholar
  10. 10.
    Seve P, Mackey J, Issac S et al (2005) 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 4:2001–2007PubMedCrossRefGoogle Scholar
  11. 11.
    Hayashi Y, Kuriyama H, Umezu H et al (2009) Class III β-tubulin expression in tumor cells is correlated with resistance to docetaxel in patients with completely resected non-small-cell lung cancer. Intern Med 48:203–208PubMedCrossRefGoogle Scholar
  12. 12.
    Volker M, Mone MJ, Kamakar P et al (2001) Sequential assembly of the nucleotide excision repair factors in vivo. Mol Cell 8:213–224PubMedCrossRefGoogle Scholar
  13. 13.
    Simon GR, Sharma S, Cantor A et al (2005) ERCC1 expression is a predictor of survival in resected patients with non-small cell lung cancer. Chest 127:978–983PubMedCrossRefGoogle Scholar
  14. 14.
    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 355:983–991PubMedCrossRefGoogle Scholar
  15. 15.
    Zheng Z, Chen T, Li X et al (2007) DNA synthesis and repair genes RRM1 and ERCC1 in lung cancer. N Engl J Med 356:800–808PubMedCrossRefGoogle Scholar
  16. 16.
    Mountain CF (1997) Revision in the International System for Staging Lung Cancer. Chest 11:1710–1717CrossRefGoogle Scholar
  17. 17.
    Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 92:205–216PubMedCrossRefGoogle Scholar
  18. 18.
    Koh Y, Jang B, Han SW et al (2010) Expression of class III beta-tubulin correlates with unfavorable survival outcome in patients with resected non-small cell lung cancer. J Thorac Oncol 5:320–325PubMedCrossRefGoogle Scholar
  19. 19.
    Skov BG, Holm B, Erreboe A et al (2010) ERCC1 and Ki67 in small cell lung carcinoma and other neuroendocrine tumors of the lung: distribution and impact on survival. J Thorac Oncol 5:453–459PubMedCrossRefGoogle Scholar
  20. 20.
    Kaira K, Endo M, Abe M et al (2010) Biologic correlation of 2-[18F]-fluoro-2-deoxy-d-glucose uptake on positron emission tomography in thymic epithelial tumors. J Clin Oncol 28:3746–3753PubMedCrossRefGoogle Scholar
  21. 21.
    Kaira K, Oriuchi N, Shimizu K et al (2008) Evaluation of thoracic tumors with 18F-FMT and 18F-FDG PET-CT: a clinicopathological study. Int J Cancer 124:1152–1160CrossRefGoogle Scholar
  22. 22.
    Kaira K, Oriuchi N, Imai H et al (2008) Prognostic significance of L-type amino acid transporter 1 expression in resectable stage I-III nonsmall cell lung cancer. Br J Cancer 98:742–748PubMedCrossRefGoogle Scholar
  23. 23.
    Davies AM, Lara PN Jr, Mack PC et al (2003) Docetaxel in non-small cell lung cancer: a review. Expert Opin Pharmacother 4:553–565PubMedCrossRefGoogle Scholar
  24. 24.
    Maio MD, Chiodini P, Georgoulias V et al (2009) Meta-analysis of single-agent chemotherapy compared with combination chemotherapy as second-line treatment of advanced non-small-cell lung cancer. J Clin Oncol 27:1836–1843PubMedCrossRefGoogle Scholar
  25. 25.
    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 98:1336–1343PubMedCrossRefGoogle Scholar
  26. 26.
    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 13:1554–1562CrossRefGoogle Scholar
  27. 27.
    Sekine I, Nokihara H, Yamamoto N et al (2009) Comparative chemotherapeutic efficacy in non-small cell lung cancer patients with postoperative recurrence and stage IV disease. J Thorac Oncol 4:518–521PubMedCrossRefGoogle Scholar

Copyright information

© Japan Society of Clinical Oncology 2012

Authors and Affiliations

  • Kyoichi Kaira
    • 1
  • Toshiaki Takahashi
    • 1
  • Haruyasu Murakami
    • 1
  • Takehito Shukuya
    • 1
  • Hirotsugu Kenmotsu
    • 1
  • Akira Ono
    • 1
  • Tateaki Naito
    • 1
  • Asuka Tsuya
    • 1
  • Yukiko Nakamura
    • 1
  • Masahiro Endo
    • 3
  • Haruhiko Kondo
    • 2
  • Takashi Nakajima
    • 4
  • Nobuyuki Yamamoto
    • 1
  1. 1.Division of Thoracic OncologyShizuoka Cancer CenterNagaizumi-cho, Sunto-gunJapan
  2. 2.Division of Thoracic SurgeryShizuoka Cancer CenterNagaizumi-cho, Sunto-gunJapan
  3. 3.Division of Diagnostic RadiologyShizuoka Cancer CenterNagaizumi-cho, Sunto-gunJapan
  4. 4.Division of Diagnostic PathologyShizuoka Cancer CenterNagaizumi-cho, Sunto-gunJapan

Personalised recommendations