title: Coexpression of EGFR and CXCR4 predicts poor prognosis in resected pancreatic ductal adenocarcinoma.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) is highly expressed in pancreatic ductal adenocarcinoma (PDAC) and is involved in tumorigenesis and development. However, EGFR expression alone has limited clinical and prognostic significance. Recently, the cross-talk between EGFR and G-protein-coupled chemokine receptor CXCR4 has become increasingly recognized.
  
  
  METHODS
  In the present study, immunohistochemical staining of EGFR and CXCR4 was performed on paraffin-embedded specimens from 131 patients with surgically resected PDAC. Subsequently, the associations between EGFR expression, CXCR4 expression, EGFR/CXCR4 coexpression and clinicopathologic factors were assessed, and survival analyses were performed.
  
  
  RESULTS
  In total, 64 (48.9%) patients expressed EGFR, 68 (51.9%) expressed CXCR4, and 33 (25.2%) coexpressed EGFR and CXCR4. No significant association between EGFR and CXCR4 expression was observed (P = 0.938). EGFR expression significantly correlated with tumor differentiation (P = 0.031), whereas CXCR4 expression significantly correlated with lymph node metastasis (P = 0.001). EGFR/CXCR4 coexpression was significantly associated with lymph node metastasis (P = 0.026), TNM stage (P = 0.048), and poor tumor differentiation (P = 0.004). By univariate survival analysis, both CXCR4 expression and EGFR/CXCR4 coexpression were significant prognostic factors for poor disease-free survival (DFS) and overall survival (OS). Moreover, EGFR/CXCR4 coexpression significantly increased the hazard ratio for both recurrence and death compared with EGFR or CXCR4 protein expression alone. Multivariate survival analysis demonstrated that EGFR/CXCR4 coexpression was an independent prognostic factor for DFS (HR = 2.33, P<0.001) and OS (HR = 2.48, P = 0.001).
  
  
  CONCLUSIONS
  In conclusion, our data indicate that although EGFR expression alone has limited clinical and prognostic significance, EGFR/CXCR4 coexpression identified a subset of PDAC patients with more aggressive tumor characteristics and a significantly worse prognosis. Our results suggest a potentially important "cross-talk" between CXCR4 and EGFR intracellular pathways and indicate that the simultaneous inhibition of these pathways might be an attractive therapeutic strategy for PDAC.
authors: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China.
authors: Huanwen
authors: H
authors: Wu
authors: Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China.
authors: Liang
authors: L
authors: Zhu
authors: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China.
authors: Hui
authors: H
authors: Zhang
authors: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China.
authors: Xiaohua
authors: X
authors: Shi
authors: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China.
authors: Li
authors: L
authors: Zhang
authors: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China.
authors: Wenze
authors: W
authors: Wang
authors: Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China.
authors: Huadan
authors: H
authors: Xue
authors: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China.
authors: Zhiyong
authors: Z
authors: Liang
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000378:metabolism*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D019718:Receptors, CXCR4; D066246:ErbB Receptors