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Prognostic value of expression of EGFR and nm23 for locoregionally advanced nasopharyngeal carcinoma

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Abstract

The purpose of this study was to evaluate the prognostic value of expression of EGFR and nm23 in patients with advanced-stage nasopharyngeal carcinoma (NPC). The study population comprised 127 patients with stage III–IVa NPC with sufficient pretreatment tumor biopsy specimens from 2003 to 2004 and clinical follow-up data. The expression of EGFR and nm23 was detected by immunohistochemistry. Survival analysis was performed using Kaplan–Meier method. The correlation between pretreatment expression of EGFR and nm23, and the effectiveness of chemoradiotherapy was analyzed. The EGFR expression was correlated with primary lesion stage and clinical stage (P = 0.001, 0.002, respectively). There was a statistically significant association between nm23 expression and local lymph node stage (P = 0.000). The positive EGFR expression had a higher recurrent rate than the negative (P = 0.015). The positive nm23 expression had a lower distant metastasis rate than the negative (P = 0.021). Negative expression of EGFR had a significantly better 5-year OS and DFS than positive expression (P = 0.015, 0.013, respectively). Positive expression of nm23 had a significantly higher 5-year OS and DFS than negative expression (P = 0.001, 0.006, respectively). Multivariate analysis indicated that both pretreatment EGFR and nm23 expression were strong independent factors for the overall survival of patients with NPC (P = 0.000, 0.000, respectively). Our data suggested that EGFR and nm23 can serve as reliable biomarkers for prognosis prediction in patients with NPC who may benefit from alternate treatment strategy and targeted treatment.

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References

  1. Licitra L, Bernier J, Cvitkovic E, Grandi C, Spinazze S, Bruzzi P, Gatta G, Molinari R. Cancer of the nasopharynx. Crit Rev Oncol Hemato. 2003;45(2):199–213.

    Article  Google Scholar 

  2. Titcomb CP Jr. High incidence of nasopharyngeal carcinoma in Asia. J Insur Med. 2001;33(3):235–8.

    PubMed  Google Scholar 

  3. Li XM, Huang WG, Yi H, Cheng AL, Xiao ZQ. Proteomic analysis to identify cytokeratin 18 as a novel biomarker of nasopharyngeal carcinoma. J Cancer Res Clin Oncol. 2009;135(12):1763–75.

    Article  PubMed  CAS  Google Scholar 

  4. Ben Nasr H, Chahed K, Remadi S, Zakhama A, Chouchane L. Expression and clinical significance of latent membrane protein-1, matrix metalloproteinase-1 and Ets-1 transcription factor in Tunisian nasopharyngeal carcinoma patients. Arch Med Res. 2009;40(3):196–203.

    Article  PubMed  CAS  Google Scholar 

  5. Thariat J, Yildirim G, Mason KA, Garden AS, Milas L, Ang KK. Combination of radiotherapy with EGFR antagonists for head and neck carcinoma. Int J Clin Oncol. 2007;12:99–110.

    Article  PubMed  CAS  Google Scholar 

  6. Chua DT, Nicholls JM, Sham JS, Au GK. Prognostic value of epidermal growth factor receptor expression in patients with advanced stage nasopharyngeal carcinoma treated with induction chemotherapy and radiotherapy. Int J Radiat Oncol Biol Phys. 2004;59(1):11–20.

    Article  PubMed  CAS  Google Scholar 

  7. Woodburn JR. The epidermal growth factor receptor and its inhibition in cancer therapy. Pharmacol Ther. 1999;82:241–50.

    Article  PubMed  CAS  Google Scholar 

  8. Putti TC, To KF, Hsu HC, Chan AT, Lai GM, Tse G, Lee YS, Whang-Peng J, Millward M, Lin L, Lin X, Lee CS. Expression of epidermal growth factor receptor in head and neck cancers correlates with clinical progression: a multicentre immunohistochemical study in the Asia–Pacific region. Histopathology. 2002;41:144–51.

    Article  PubMed  CAS  Google Scholar 

  9. Steeg PS, Bevilacqua G, Kopper L, Thorgeirsson UP, Talmadge JE, Liotta LA, Sobel ME. Evidence for a novel gene associated with low tumor metastatic potential. J Natl Cancer Inst. 1988;80:200–4.

    Article  PubMed  CAS  Google Scholar 

  10. Kawakubo Y, Sato Y, Koh T, Kono H, Kameya T. Expression of nm23 protein in pulmonary adenocarcinomas: inverse correlation to tumor progression. LungCancer. 1997;17:103–13.

    CAS  Google Scholar 

  11. Ohta Y, Nozawa H, Tanaka Y, Oda M, Watanabe Y. Increased vascular endothelial growth factor and vascular endothelial growth factor-C and decreased nm23 expression associated with microdissemination in the lymph nodes in stage I non-small cell lung cancer. J Thorac Cardiovasc Surg. 2000;119:804–13.

    Article  PubMed  CAS  Google Scholar 

  12. Guo X, Min HQ, Zeng MS, Qian CN, Huang XM, Shao JY, Hou JH. Nm23-H1 expression in nasopharyngeal carcinoma: correlation with clinical outcome. Int J Cancer. 1998;79(6):596–600.

    Article  PubMed  CAS  Google Scholar 

  13. Lee AW, Tung SY, Chua DT. Randomized trial of radiotherapy plus concurrent-adjuvant chemotherapy vs radiotherapy alone for regionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst. 2010;102(15):1188–98.

    Article  PubMed  Google Scholar 

  14. Al-Sarraf M, LeBlanc M, Giri PG, Fu KK, Cooper J, Vuong T, Forastiere AA, Adams G, Sakr WA, Schuller DE, Ensley JF. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized intergroup study 0099. J Clin Oncol. 1998;16:1310–7.

    PubMed  CAS  Google Scholar 

  15. Chen Y, Liu MZ, Liang SB, Zong JF, Mao YP, Tang LL, Guo Y, Lin AH, Zeng XF, Ma J. Preliminary results of a prospective randomized trial comparing concurrent chemoradiotherapy plus adjuvant chemotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma in endemic regions of china. Int J Radiat Oncol Biol Phys. 2008;71(5):1356–64.

    Article  PubMed  Google Scholar 

  16. Chan AT, Leung SF, Ngan RK, Teo PM, Lau WH, Kwan WH, Hui EP, Yiu HY, Yeo W, Cheung FY, Yu KH, Chiu KW, Chan DT, Mok TS, Yau S, Yuen KT, Mo FK, Lai MM, Ma BB, Kam MK, Leung TW, Johnson PJ, Choi PH, Zee BC. Overall survival after concurrent cisplatin-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst. 2005;97:536–9.

    Article  PubMed  CAS  Google Scholar 

  17. Lee AW, Tung SY, Chan AT, Chappell R, Fu YT, Lu TX, Tan T, Chua DT, O’sullivan B, Xu SL, Pang ES, Sze WM, Leung TW, Kwan WH, Chan PT, Liu XF, Tan EH, Sham JS, Siu L, Lau WH. Preliminary results of a randomized study (NPC-9902 Trial) on therapeutic gain by concurrent chemotherapy and/or accelerated fractionation for locally advanced nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2006;66(1):142–51.

    Article  PubMed  Google Scholar 

  18. Bourhis J, Overgaard J, Audry H, Ang KK, Saunders M, Bernier J, Horiot JC, Le Maître A, Pajak TF, Poulsen MG, O’Sullivan B, Dobrowsky W, Hliniak A, Skladowski K, Hay JH, Pinto LH, Fallai C, Fu KK, Sylvester R, Pignon JP. Hyperfractionated or accelerated radiotherapy in head and neck cancer: a metaanalysis. Lancet. 2006;368:843–54.

    Article  PubMed  Google Scholar 

  19. Caponigro F, Longo F, Ionna F, Perri F. Treatment approaches to nasopharyngeal carcinoma: a review. Anticancer Drugs. 2010;21(5):471–7.

    Article  PubMed  CAS  Google Scholar 

  20. Lin S, Lu JJ, Han L, Chen Q, Pan J. Sequential chemotherapy and intensity-modulated radiation therapy in the management of locoregionally advanced nasopharyngeal carcinoma: experience of 370 consecutive cases. BMC Cancer. 2010;10:39.

    Article  PubMed  Google Scholar 

  21. Yoshida T, Zhang G, Haura EB. Targeting epidermal growth factor receptor: central signaling kinase in lung cancer. Biochem Pharmacol. 2010;80(5):613–23.

    Article  PubMed  CAS  Google Scholar 

  22. de La Motte Rouge T, Valent A, Ambrosetti D, Vielh P, Lacroix L. Clinical and molecular predictors of response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer. Ann Pathol. 2007;27:353–63.

    Article  Google Scholar 

  23. Ang KK, Berkey BA, Tu X, Zhang HZ, Katz R, Hammond EH, Fu KK, Milas L. Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma. Cancer Res. 2002;62:7350–6.

    PubMed  CAS  Google Scholar 

  24. Wen QH, Miwa T, Yoshizaki T. Prognostic value of EGFR and TGF-alpha in early laryngeal cancer treated with radiotherapy. Laryngoscope. 1996;106:884–8.

    Article  PubMed  CAS  Google Scholar 

  25. Lee CS, Redshaw A, Boag G. Epidermal growth factor immunoreactivity in human laryngeal squamous cell carcinoma. Pathology. 1997;29:251–4.

    Article  PubMed  CAS  Google Scholar 

  26. Maurizi M, Almadori G, Ferrandina G. Prognostic significance of epidermal growth factor receptor in laryngeal squamous cell carcinoma. Br J Cancer. 1996;74:1253–7.

    Article  PubMed  CAS  Google Scholar 

  27. Grandis JR, Melhem MF, Gooding WE. Levels of TGF-alpha and EGFR protein in head and neck squamous cell carcinoma and patient survival. J Natl Cancer Inst. 1998;90:824–32.

    Article  Google Scholar 

  28. Ma B, Hui EP, King A, To KF, Mo F, Leung SF, Kam M, Lo YM, Zee B, Mok T, Ahuja A, Chan AT. A phase II study of patients with metastatic or locoregionally recurrent nasopharyngeal carcinoma and evaluation of plasma Epstein–Barr virus DNA as a biomarker of efficacy. Cancer Chemother Pharmacol. 2008;62(1):59–64.

    Article  PubMed  CAS  Google Scholar 

  29. Taheri-Kadkhoda Z, Magnusson B, Svensson M, Mercke C, Björk-Eriksson T. Expression modes and clinical manifestations of latent membrane protein 1, Ki-67, cyclin-B1, and epidermal growth factor receptor in nonendemic nasopharyngeal carcinoma. Head Neck. 2009;31(4):482–92.

    Article  PubMed  Google Scholar 

  30. Cojocariu OM, Huguet F, Lefevre M, Périé S. Prognosis and predictive factors in head-and-neck cancers. Bull Cancer. 2009;96(4):369–78.

    PubMed  CAS  Google Scholar 

  31. Geoerger B, Gaspar N, Opolon P, Morizet J, Devanz P, Lecluse Y, Valent A, Lacroix L, Grill J, Vassal G. EGFR tyrosine kinase inhibition radiosensitizes and induces apoptosis in malignant glioma and childhood ependymoma xenografts. Int J Cancer. 2008;123(1):209–16.

    Article  PubMed  CAS  Google Scholar 

  32. Ping Y, Jian Z, Yi Z, Huoyu Z, Feng L, Yuqiong Y, Shixi L. Inhibition of the EGFR with nanoparticles encapsulating antisense oligonucleotides of the EGFR enhances radiosensitivity in SCCVII cells. Med Oncol. 2010;27(3):715–21.

    Article  PubMed  CAS  Google Scholar 

  33. Chen CC, Chen WC, Lu CH, Wang WH, Lin PY, Lee KD, Chen MF. Significance of interleukin-6 signaling in the resistance of pharyngeal cancer to irradiation and the epidermal growth factor receptor inhibitor. Int J Radiat Oncol Biol Phys. 2010;76(4):1214–24.

    Article  PubMed  CAS  Google Scholar 

  34. Choi EJ, Ryu YK, Kim SY, Wu HG, Kim JS, Kim IH, Kim IA. Targeting epidermal growth factor receptor-associated signaling pathways in non-small cell lung cancer cells: implication in radiation response. Mol Cancer Res. 2010;8(7):1027–36.

    Article  PubMed  CAS  Google Scholar 

  35. Akimoto T. Molecular basis and clinical results of radiation therapy combined with molecular targeted therapy. Nippon Rinsho. 2010;68(6):1025–34.

    PubMed  Google Scholar 

  36. Kim JE, Lee DH, Choi Y, Yoon DH, Kim SW, Suh C, Lee JS. Epidermal growth factor receptor tyrosine kinase inhibitors as a first-line therapy for never-smokers with adenocarcinoma of the lung having asymptomatic synchronous brain metastasis. Lung Cancer. 2009;65(3):351–4.

    Article  PubMed  Google Scholar 

  37. Bernier J, Bonner J, Vermorken JB, Bensadoun RJ, Dummer R, Giralt J, Kornek G, Hartley A, Mesia R, Robert C, Segaert S, Ang KK. Consensus guidelines for the management of radiation dermatitis and coexisting acne-like rash in patients receiving radiotherapy plus EGFR inhibitors for the treatment of squamous cell carcinoma of the head and neck. Ann Oncol. 2008;19(1):142–9.

    Article  PubMed  CAS  Google Scholar 

  38. Cripps C, Winquist E, Devries MC, Stys-Norman D, Gilbert R. Epidermal growth factor receptor targeted therapy in stages III and IV head and neck cancer. Curr Oncol. 2010;17(3):37–48.

    Article  PubMed  CAS  Google Scholar 

  39. Razak AR, Siu LL, Le Tourneau C. Molecular targeted therapies in all histologies of head and neck cancers: an update. Curr Opin Oncol. 2010;22(3):212–20.

    Article  PubMed  CAS  Google Scholar 

  40. Sgouros J, Galani E, Gonos E, Moutsatsou P, Belechri M, Skarlos D, Dionyssiou-Asteriou A. Correlation of nm23-H1 gene expression with clinical outcome in patients with advanced breast cancer. In Vivo. 2007;21(3):519–22.

    PubMed  CAS  Google Scholar 

  41. Pasz-Walczak G, Salagacka A, Potemski P, Balcerczak E, Kordek R, Mirowski M. Maspin and Nm23-H1 expression in colorectal cancer. Neoplasma. 2010;57(2):95–101.

    Article  PubMed  CAS  Google Scholar 

  42. Guo H, Nan K, Hu T, Meng J, Hui W, Zhang X, Qin H, Sui C. Prognostic significance of co-expression of nm23 and p57 protein in hepatocellular carcinoma. Hepatol Res. 2010. doi:10.1111/j.1872-034X.2010.00721.x.

    Google Scholar 

  43. Tham IW, Lu JJ. Controversies and challenges in the current management of nasopharyngeal cancer. Expert Rev Anticancer Ther. 2010;10(9):1439–50.

    Article  PubMed  Google Scholar 

  44. Huang GW, Mo WN, Kuang GQ, Nong HT, Wei MY, Sunagawa M, Kosugi T. Expression of p16, nm23-H1, E-cadherin, and CD44 gene products and their significance in nasopharyngeal carcinoma. Laryngoscope. 2001;111(8):1465–71.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Jun Fang Hao.

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Cao, X.J., Hao, J.F., Yang, X.H. et al. Prognostic value of expression of EGFR and nm23 for locoregionally advanced nasopharyngeal carcinoma. Med Oncol 29, 263–271 (2012). https://doi.org/10.1007/s12032-010-9782-y

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  • DOI: https://doi.org/10.1007/s12032-010-9782-y

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