Association of CXCR4 and CCR7 chemokine receptor expression and lymph node metastasis in human cervical cancer.
BACKGROUND
The chemokine receptors CXCR4 and CCR7 have been suggested to play an important role in cancer invasion and metastasis. The expression of these receptors in human cervical cancer, however, has seldom been characterized.


METHODS
We investigated the expression of CXCR4 and CCR7 in cervical cancer specimens and determined the association between their expression and the clinicopathological features observed, including patient outcome.


RESULTS
CXCR4 expression was significantly higher in elderly patients (P=0.025); it was also significantly increased in patients with cancers displaying large tumor size (P=0.010), deep stromal invasion (P=0.0004), lymph-vascular space involvement (P=0.0002), or lymph node metastasis (P<0.0001). CCR7 expression was significantly higher in cases of squamous cell carcinomas (P=0.010) and in patients with cancers showing large tumor size (P<0.0001), deep stromal invasion (P<0.0001), vaginal invasion (P=0.047), lymph-vascular space involvement (P=0.012), or lymph node metastasis (P<0.0001). Logistic regression analysis revealed that deep stromal invasion (P=0.017) and CXCR4 (P=0.016) and CCR7 (P=0.022) expression were independent factors that influenced pelvic lymph node metastasis. The disease-free survival and overall survival (OS) rates of patients exhibiting both CXCR4 and CCR7 expression were significantly reduced (P<0.0001). In addition, the expression of both CXCR4 and CCR7 was an independent prognostic factor for OS (95% confidence interval=1.03-17.86; P=0.046).


CONCLUSIONS
CXCR4 and CCR7 expression may be associated with lymph node metastasis; moreover, the expression of these receptors can serve as an indicator of poor prognosis in patients with cervical cancer.
Kodama
J
J
Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. Electronic address: kodama@cc.okayama-u.ac.jp.
Hasengaowa
Department of Obstetrics and Gynecology, Inner Mongolia Agriculture University Hospital, Huhehaote, China.
Kusumoto
T
T
Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Seki
N
N
Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Matsuo
T
T
Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Ojima
Y
Y
Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Nakamura
K
K
Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Hongo
A
A
Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Hiramatsu
Y
Y
Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000556:secondary; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D054400:Receptors, CCR7; D019718:Receptors, CXCR4 / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
C515370:CCR7 protein, human; D054400:Receptors, CCR7; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine