Esophageal Cancer
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Dec 21, 2006; 12(47): 7585-7590
Published online Dec 21, 2006. doi: 10.3748/wjg.v12.i47.7585
Persistent CXCR4 expression after preoperative chemoradiotherapy predicts early recurrence and poor prognosis in esophageal cancer
Kenji Koishi, Reigetsu Yoshikawa, Tohru Tsujimura, Tomoko Hashimoto-Tamaoki, Syoudou Kojima, Hidenori Yanagi, Takehira Yamamura, Yoshinori Fujiwara
Kenji Koishi, Reigetsu Yoshikawa, Syoudou Kojima, Hidenori Yanagi, Takehira Yamamura, Yoshinori Fujiwara, Second Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
Reigetsu Yoshikawa, Tomoko Hashimoto-Tamaoki, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
Tohru Tsujimura, Second Department of Pathology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
Tomoko Hashimoto-Tamaoki, Department of Genetics, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
Author contributions: All authors contributed equally to the work.
Supported by grants from the Medical Research Fund of Hyogo Medical Association
Correspondence to: Reigetsu Yoshikawa, MD, PhD, Second Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan. yosikr2s@hyo-med.ac.jp
Telephone: +81-798-456372 Fax: +81-798-456373
Received: August 23, 2006
Revised: September 18, 2006
Accepted: September 24, 2006
Published online: December 21, 2006
Abstract

AIM: To study the effect of CXC chemokine receptor-4 (CXCR4) expression on disease progression and prognosis in esophageal cancer.

METHODS: CXCR4 expression was evaluated in 37 patients with histologically confirmed esophageal squamous carcinomas (ESCC) undergoing preoperative chemoradiotherapy (CRT) by immunohistochemical staining.

RESULTS: Eleven out of 37 ESCC patients showed a pathological complete response (CR) after CRT. CXCR4 protein expression was observed in cell cytoplasms of 13 tumors, and null expression was seen in 13 tumors. Distant recurrence was significantly more common in patients with positive CXCR4 expression (P = 0.0318). After a median follow-up time of 31.6 mo, 19 patients progressed (12 of 19 expressed positive CXCR4) and 11 died (10 of 11 expressed positive CXCR4). Overall survival was significantly correlated with lymph node metastasis (952.1 ± 53.8 d in negative group vs 475.1 ± 56.2 d in positive group, P = 0.023), distant metastasis (874.0 ± 60.4 d in negative group vs 434.9 ± 75.2 d in positive group, P = 0.014) and CRT (811.5 ± 51.2 d in responder group vs 459.6 ± 94.0 d in non-responder group, P = 0.00038) and further with an absence of CXCR4 expression or no residual tumor (959.8 ± 51.0 d in null expression or no tumor group vs 412.0 ± 57.1 d in positive expression group, P = 0.0001).

CONCLUSION: Persistent positive CXCR4 expression is implicated in tumor aggressiveness and poor prognosis in ESCC after CRT, and preoperative CRT may improve the prognosis of ESCC via CXCL12-CXCR4 signaling pathway.

Keywords: CXC chemokine receptor-4, Metastasis, Chemoradiotherapy, Esophageal cancer