Persistent CXCR4 expression after preoperative chemoradiotherapy predicts early recurrence and poor prognosis in esophageal cancer.
OBJECTIVE
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).


CONCLUSIONS
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.
Koishi
Kenji
K
Second Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
Yoshikawa
Reigetsu
R
Tsujimura
Tohru
T
Hashimoto-Tamaoki
Tomoko
T
Kojima
Syoudou
S
Yanagi
Hidenori
H
Yamamura
Takehira
T
Fujiwara
Yoshinori
Y
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000378:metabolism; D011237:Predictive Value of Tests; D011300:Preoperative Care; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000378:metabolism*; D012307:Risk Factors
D014408:Biomarkers, Tumor; D019718:Receptors, CXCR4