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Annals of Surgical Oncology

, Volume 13, Issue 12, pp 1724–1731 | Cite as

REG I Expression Predicts Long-term Survival among Locally Advanced Thoracic Squamous Cell Esophageal Cancer Patients Treated with Neoadjuvant Chemoradiotherapy Followed by Esophagectomy

  • Satoru Motoyama
  • Toshihiro Sugiyama
  • Yasuharu Ueno
  • Hiroshi Okamoto
  • Shin Takasawa
  • Hiroshi Nanjo
  • Hitoshi Watanabe
  • Kiyotomi Maruyama
  • Manabu Okuyama
  • Jun-ichi Ogawa
Article

Abstract

Background

The prognosis for patients with locally advanced thoracic esophageal cancer is extremely unfavorable. We have been administering neoadjuvant chemoradiotherapy (CRT) followed by esophagectomy to these patients and studying whether REG I expression in untreated endoscopic biopsy specimens is predictive of patient responsiveness to CRT and/or survival after treatment.

Methods

Between 1992 and 2003, 47 patients with T4 (direct invasion of adjacent organs) thoracic esophageal cancers were administered neoadjuvant CRT followed by esophagectomy. REG I expression was assessed in untreated endoscopic biopsy specimens and correlated with clinical and histological responses and survival in 37 patients who had also undergone curative surgery.

Results

Among the 37 cases that received CRT followed by surgery, the therapeutic response rate for neoadjuvant CRT was 68%, and a complete histological response in resected specimens from the primary lesion was achieved in 8 (22%) patients. These clinical and histological responses to neoadjuvant CRT did not significantly correlate with survival, however. By contrast, 9 patients were judged REG-positive based on analysis of their untreated endoscopic biopsy specimens, and their cumulative survival rate was significantly higher than that of the 28 REG-negative patients (P = 0.0073). Univariate analysis showed REG I expression to be a prognostic factor (P = 0.0386) that increased the risk of death 8.4-fold.

Conclusions

Evaluation of REG I expression in untreated endoscopic biopsy specimens may provide a basis for new treatments of locally advanced thoracic squamous cell esophageal cancers.

Keywords

Esophageal cancer Chemoradiotherapy Esophagectomy REG I Prognosis 

References

  1. 1.
    Abo S, Kitamura M, Hashimoto M, et al. Analysis of results of surgery performed over a 20-year period on 500 patients with cancer of the thoracic esophagus. Surg Today 1996; 26:77–82PubMedCrossRefGoogle Scholar
  2. 2.
    Ando N, Ozawa S, Kitagawa Y, Shinozawa Y, Kitajima M. Improvement in the results of surgical treatment of advanced squamous esophageal carcinoma during 15 consecutive years. Ann Surg 2000; 232:225–32PubMedCrossRefGoogle Scholar
  3. 3.
    Motoyama S, Saito R, Kamata S, et al. Survival advantage of using autologous blood transfusion during surgery for esophageal cancer. Surg Today 2002; 32:951–8PubMedCrossRefGoogle Scholar
  4. 4.
    Ohtsu A, Boku N, Muro K, et al. Definitive chemoradiotherapy for T4 and/or M1 lymph node squamous cell carcinoma of the esophagus. J Clin Oncol 1999; 17:2915–21PubMedGoogle Scholar
  5. 5.
    Hironaka S, Ohtsu A, Boku N, et al. Nonrandomized comparison between definitive chemoradiotherapy and radical surgery in patients with T(2–3)N(any) M(0) squamous cell carcinoma of the esophagus. Int J Radiat Oncol Biol Phys 2003; 57:425–33PubMedCrossRefGoogle Scholar
  6. 6.
    Terazono K, Yamamoto H, Takasawa S, Shiga K, Yonemura Y, Tochino Y, Okamoto H. A novel gene activated in regenerating islets. J Biol Chem 1988; 263:2111–4PubMedGoogle Scholar
  7. 7.
    Watanabe T, Yonekura H, Yonemura Y, et al. Pancreatic beta-cell replication and amelioration of surgical diabetes by Reg protein. Proc Natl Acad Sci USA 1994; 91:3589–92PubMedCrossRefGoogle Scholar
  8. 8.
    Bernard-Perrone FR, Renaud WP, Guy-Crottee OM, et al. Expression of REG protein during cell growth and differentiation of two human colon carcinoma cell lines. J Histochem Cytochem 1999; 47:863–70PubMedGoogle Scholar
  9. 9.
    Christa L, Carrnot F, Simon MT, et al. HIP/PAP is an adhesion protein expressed in hepatocarcinoma, normal Paneth, and pancreatic cells. Am J Physiol 1996; 271:G993–G02PubMedGoogle Scholar
  10. 10.
    Yonemura Y, Sakurai S, Yamamoto H, et al. REG gene expression is associated with the infiltrating growth of gastric carcinoma. Cancer 2003; 98:1394–00PubMedCrossRefGoogle Scholar
  11. 11.
    Kadowaki Y, Ishihara S, Miyaoka Y, et al. Reg protein is overexpressed in gastric cancer cells, where it activates a signal transduction pathway that converges on ERK1/2 to stimulate growth. FEBS Lett 2002; 530:59–64PubMedCrossRefGoogle Scholar
  12. 12.
    Japanese Society for Esophageal Diseases. Guidelines for the Clinical and Pathologic Studies on Carcinoma of the Esophagus. 9th edn. Kanehara Public Co, Tokyo. 1999Google Scholar
  13. 13.
    Fujita H, Sueyoshi S, Tanaka T, et al. Prospective non-randomized trial comparing esophagectomy-followed-by-chemoradiotherapy versus chemoradiotherapy-followed-by-esophagectomy for T4 esophageal cancers. J Surg Oncol 2005; 90:209–19PubMedCrossRefGoogle Scholar
  14. 14.
    Greer SE, Doodney PP, Sutton JE, Birkmeyer JD. Neoadjuvant chemoradiotherapy for esophageal carcinoma: a meta-analysis. Surgery 2005; 137:172–7PubMedCrossRefGoogle Scholar
  15. 15.
    Chan ACW, Lee DWH, Griffith JF, et al. The clinical efficacy of neoadjuvant chemotherapy in squamous esophageal cancer: a prospective nonrandomized study of pulse and continuous-infusion regimens with cisplatin and 5-fluorouracil. Ann Surg Oncol 2002; 9:617–24PubMedCrossRefGoogle Scholar
  16. 16.
    Takeuchi H, Ozawa S, Ando N, Kitagawa Y, Ueda M, Kitajima M. Cell-cycle regulators and the Ki-67 labeling index can predict the response to chemoradiotherapy and the survival of patients with locally advanced squamous cell carcinoma of the esophagus. Ann Surg Oncol 2003; 10:792–00PubMedCrossRefGoogle Scholar
  17. 17.
    Kesler KA, Helft PR, Werner EA, et al. A retrospective analysis of locally advanced esophageal cancer patients treated with neoadjuvant chemoradiation therapy followed by surgery or surgery alone. Ann Thorac Surg 2005; 79:1116–21PubMedCrossRefGoogle Scholar
  18. 18.
    Nakayama K, Kanzaki A, Terada K, et al. Prognostic value of the Cu-transporting ATPase in ovarian carcinoma patients receiving cisplatin-based chemotherapy. Clin Cancer Res 2004; 10:2804–11PubMedCrossRefGoogle Scholar
  19. 19.
    Francis PJ, Southgate JL, Wilkin TJ, Bone AJ. Expression of an islet regeneration (reg) gene in isolated rat islets: effects of nutrient and non-nutrient growth factors. Diabetologia 1992; 35:238–42PubMedCrossRefGoogle Scholar
  20. 20.
    Watanabe T, Yonekura H, Terazono K, Yamamoto H, Okamoto H. Complete nucleotide sequence of human reg gene and its expression in normal and tumoral tissues. J Biol Chem 1990; 265:7432–39PubMedGoogle Scholar
  21. 21.
    Macadam RCA, Sarela AI, Farmey SM, Robinson PA, Markham AF, Guillou PJ. Death from early colorectal cancer is predicted by the presence of transcripts of the REG gene family. Br J Cancer 2000; 83:188–95PubMedCrossRefGoogle Scholar
  22. 22.
    Harada K, Zen Y, Kanemori Y, et al. Human REG I gene is up-regulated in intrahepatic cholangiocarcinoma and its precursor lesions. Hepatology 2001; 33:1036–42PubMedCrossRefGoogle Scholar
  23. 23.
    Geh JI, Crellin AM, Glynne-Jones R. Preoperative (neoadjuvant) chemoradiotherapy in oesophageal cancer. Br J Surg 2001; 88:338–356PubMedCrossRefGoogle Scholar
  24. 24.
    Slater MS, Holland J, Faigel DO, Sheppard BC, Deveney CW. Does neoadjuvant chemoradiation downstage esophageal carcinoma? Am J Surg 2001; 181:440–4PubMedCrossRefGoogle Scholar
  25. 25.
    Ikeda K, Ishida K, Sato N, et al. Chemoradiotherapy followed by surgery for thoracic esophageal cancer potentially or actually involving adjacent organs. Dis Esophagus 2001; 14:197–01PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2006

Authors and Affiliations

  • Satoru Motoyama
    • 1
  • Toshihiro Sugiyama
    • 2
  • Yasuharu Ueno
    • 2
  • Hiroshi Okamoto
    • 3
  • Shin Takasawa
    • 4
  • Hiroshi Nanjo
    • 5
  • Hitoshi Watanabe
    • 6
  • Kiyotomi Maruyama
    • 1
  • Manabu Okuyama
    • 1
  • Jun-ichi Ogawa
    • 1
  1. 1.Department of SurgeryAkita University School of MedicineAkitaJapan
  2. 2.Department of BiochemistryAkita University School of MedicineAkitaJapan
  3. 3.Department of Advanced Biological Sciences for Regeneration (Kotobiken Medical Laboratories)Tohoku University Graduate School of MedicineSendaiJapan
  4. 4.Department of BiochemistryTohoku University Graduate School of MedicineSendaiJapan
  5. 5.Department of PathologyAkita University School of MedicineAkitaJapan
  6. 6.Central Research LaboratoryAkita University School of MedicineAkitaJapan

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