title: Nuclear expression of chemokine receptor CXCR4 indicates poorer prognosis in gastric cancer.
abstract: BACKGROUND
  The CXCL12/CXCR4 axis plays a pivotal role in cancer progression and metastases in various epithelial cancer cells. The aim of the present study was to evaluate the localization and correlation between CXCL12/CXCR4 expression and clinicopathological features in gastric cancers.
  
  
  METHODS
  This study included 111 Japanese patients with primary gastric cancers, which invade submucosa or more, all of whom underwent gastrectomy between 1992 and 1996. Immunohistochemical analysis was performed.
  
  
  RESULTS
  A significant correlation was found in the immunoreactivity of nuclear CXCR4 and poor differentiation (p=0.0026), infiltrated pattern (p<0.0001), larger size (p<0.0001), advanced stage (p=0.0342) and reduced 5-year survival rate (30% vs. 61%, p=0.0012). Multivariate analysis revealed that high nuclear CXCR4 immunoreactivity (RR: 3.077, p=0.0329) retained its strength as an independent prognostic factor for overall survival.
  
  
  CONCLUSIONS
  High immunoreactivity of nuclear CXCR4 in gastric cancer suggests that CXCL12 binds to its unique receptor CXCR4 at the membrane, translocates to the nucleus and then becomes more invasive, and thus can be considered a prognostic factor.
authors.affiliation: Department of Surgery and Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan nbmasuda@surg2.med.kyushu-u.ac.jp.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Masuda
authors.affiliation: Department of Surgery and Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Nakashima
authors.affiliation: Department of Surgery and Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ando
authors.affiliation: Department of Surgery and Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Yoshinaga
authors.affiliation: Department of Surgery and Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saeki
authors.affiliation: Department of Surgery and Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Oki
authors.affiliation: Department of Surgery and Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Morita
authors.affiliation: Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
authors.affiliation: Department of Surgery and Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D054377:Chemokine CXCL12 / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D005743:Gastrectomy; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010534:Peritoneal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4
keywords: CXCL12; immunohistochemistry; translocation