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

¹ Department of Surgery, Akita University School of Medicine, Akita, Japan
² Department of Biochemistry, Akita University School of Medicine, Akita, Japan
³ Department of Advanced Biological Sciences for Regeneration (Kotobiken Medical Laboratories), Tohoku University Graduate School of Medicine, Sendai, Japan
⁴ Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan
⁵ Department of Pathology, Akita University School of Medicine, Akita, Japan
⁶ Central Research Laboratory, Akita University School of Medicine, Akita, Japan

Correspondence: Address correspondence and reprint requests to: Satoru Motoyama, MD; E-mail: motoyama{at}doc.med.akita-u.ac.jp

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.

Key Words: Esophageal cancer • Chemoradiotherapy • Esophagectomy • REG I • Prognosis

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