title: Expression of CXCL12 and its receptor CXCR4 correlates with lymph node metastasis in submucosal esophageal cancer.
abstract: OBJECTIVE
  The chemokine CXCL12 and its receptor CXCR4 are involved in cell migration, proliferation, and angiogenesis, and promote organ-specific localization of distant metastases in various carcinomas. We examined their expression and microvessel density (MVD) in submucosal esophageal squamous cell carcinoma (ESCC) and analyzed their connection to clinicopathological findings including lymph node micrometastasis (LMM).
  
  
  METHODS
  Eighty-six patients with submucosal ESCC underwent curative resection from 1985 to 2002. Immunohistochemical staining of CXCL12, CXCR4, and CD34 was performed with primary tumors, and staining of cytokeratin was performed with dissected lymph nodes. MVD was calculated from CD34 expression, and LMM detected by cytokeratin staining.
  
  
  RESULTS
  Expression of CXCL12, but not CXCR4, correlated with lymph node metastasis. There was no significant correlation between the expression of CXCL12 and/or CXCR4 and MVD. LMM was detected in 8 cases and 14 lymph nodes. CXCL12 expression and high MVD were found in tumors with lymph node metastasis including LMM. Furthermore, in the CXCR4-positive tumors, positive CXCL12 expression was more significantly correlated with lymph node metastasis and/or LMM than negative CXCL12 expression.
  
  
  CONCLUSIONS
  Evaluation of CXCL12 and CXCR4 expression should assist detection of lymph node metastasis including LMM in submucosal ESCC.
authors.affiliation: Department of Surgical Oncology and Digestive Surgery, Field of Oncology, Course of Advanced Therapeutics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan. k-sasaki@m.kufm.kagoshima-u.ac.jp
authors.forename: Ken
authors.initials: K
authors.lastname: Sasaki
authors.forename: Shoji
authors.initials: S
authors.lastname: Natsugoe
authors.forename: Sumiya
authors.initials: S
authors.lastname: Ishigami
authors.forename: Masataka
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okumura
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Setoyama
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Uchikado
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kita
authors.forename: Kiyokazu
authors.initials: K
authors.lastname: Tamotsu
authors.forename: Toshihide
authors.initials: T
authors.lastname: Sakurai
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Owaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Aikou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D054377:Chemokine CXCL12 / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D016629:Esophagectomy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D019718:Receptors, CXCR4 / Q000378:metabolism*; D012189:Retrospective Studies
chemical_list: D018952:Antigens, CD34; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4