Expression of CXCL12 and its receptor CXCR4 correlates with lymph node metastasis in submucosal esophageal cancer.
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.
Sasaki
Ken
K
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
Natsugoe
Shoji
S
Ishigami
Sumiya
S
Matsumoto
Masataka
M
Okumura
Hiroshi
H
Setoyama
Tetsuro
T
Uchikado
Yasuto
Y
Kita
Yoshiaki
Y
Tamotsu
Kiyokazu
K
Sakurai
Toshihide
T
Owaki
Tetsuhiro
T
Aikou
Takashi
T
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
D018952:Antigens, CD34; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4