Expression of chemokine receptor CXCR4 in esophageal squamous cell and adenocarcinoma.
BACKGROUND
Prognosis of esophageal cancer is poor despite curative surgery. The chemokine receptor CXCR4 has been proposed to distinctly contribute to tumor growth, dissemination and local immune escape in a limited number of malignancies. The aim of our study was to evaluate the role of CXCR4 in tumor spread of esophageal cancer with a differentiated view of the two predominant histologic types--squamous cell and adenocarcinoma.


METHODS
Esophageal cancer tissue samples were obtained from 102 consecutive patients undergoing esophageal resection for cancer with curative intent. The LSAB+ System was used to detect the protein CXCR4. Tumor samples were classified into two groups based on the homogeneous staining intensity. A cut-off between CXCR4w (= weak expression) and CXCR4s (= strong expression) was set at 1.5 (grouped 0-1.5 versus 2.0-3). Long-term survival rates were calculated using life tables and the Kaplan-Meier method. Using the Cox's proportional hazards analysis, a model of survival prediction was established.


RESULTS
The overall expression rate for CXCR4 in esophageal squamous cell carcinoma was 94.1%. Subdividing these samples, CXCR4w was found in 54.9% and CXCR4s in 45.1%. In adenocarcinoma, an overall expression rate of 89.1% was detected with a weak intensitiy in 71.7% compared to strong staining in 29.3% (p = 0.066 squamous cell versus adenocarcinoma). The Cox's proportional hazards analysis identified the pM-category with a hazard ratio (HR) of 1.860 (95% CI: 1.014-3.414) (p = 0.045), the histologic tumor type (HR: 0.334; 95% CI: 0.180-0.618) (p = 0.0001) and the operative approach (transthoracic > transhiatal esophageal resection) (HR: 0.546; 95% CI: 0.324-0.920) (p = 0.023) as independent factors with a possible influence on the long-term prognosis in patients with esophageal carcinoma, whereas CXCR4 expression was statistically not significant (>0.05).


CONCLUSIONS
Expression of the chemokine receptor CXCR4 in esophageal cancer is of major relevance in both histologic entities--squamous cell and adenocarcinoma. Though with lack of statistical significance, strong CXCR4 expression revealed a poorer long-term prognosis following curative esophagectomy in both histologic subtypes. Thus, the exact biological functions of CXCR4 in terms of tumor dissemination of esophageal cancer is yet undetermined. Inhibition of esophageal cancer progression by CXCR4 antagonists might be a promising therapeutic option in the future.
Gockel
Ines
I
Department of General and Abdominal Surgery, Johannes Gutenberg-University, Mainz, Germany. gockel@ach.klinik.uni-mainz.de
Schimanski
Carl C
CC
Heinrich
Christian
C
Wehler
T
T
Frerichs
K
K
Drescher
Daniel
D
von Langsdorff
Christian
C
Domeyer
Mario
M
Biesterfeld
Stefan
S
Galle
Peter R
PR
Junginger
Theodor
T
Moehler
Markus
M
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D016629:Esophagectomy; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000235:genetics
D014408:Biomarkers, Tumor; D019718:Receptors, CXCR4