© 2005 Oxford University Press
ARTICLE |
Tumor-Cell Homing to Lymph Nodes and Bone Marrow and CXCR4 Expression in Esophageal Cancer
Affiliations of authors: Klinik fuer Allgemein-, Viszeral- und Thoraxchirurgie (JTK, EFY, PS, DO, RW, PB, AH, JRI), Institut fuer Tumorbiologie (KP), Universitaetsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany
Correspondence to: Jussuf T. Kaifi, MD, Klinik fuer Allgemein-, Viszeral- und Thoraxchirurgie, Universitaetsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany (e-mail: jkaifi{at}uke.uni-hamburg.de).
Background: The chemokine and bone marrow-homing receptor CXCR4 has been implicated in metastatic dissemination of various cancers. We investigated CXCR4 expression in esophageal cancer specimens and its association with survival, lymph node microinvolvement, and bone marrow micrometastasis. Methods: We analyzed frozen tumor specimens from 136 patients with completely resected esophageal cancer for CXCR4 expression by immunohistochemistry. Lymph node microinvolvement and bone marrow micrometastasis were assessed by immunohistochemistry with monoclonal antibodies Ber-EP4 (against epithelial cell adhesion molecule) and pancytokeratin A45-B/B3 (against several cytokeratins), respectively. Associations between CXCR4 expression and clinicopathologic features, including tumor stage, histologic grade, lymph node metastasis and microinvolvement, bone marrow micrometastasis, and survival, were investigated with Fisher's test, log-rank test, and Cox multivariable analysis. All statistical tests were two-sided. Results: CXCR4 protein was expressed in 75 (55%) of 136 esophageal tumors examined. CXCR4 expression was statistically significantly associated with reduced median overall and disease-specific survival, compared with CXCR4 nonexpression (P<.001; log-rank test). The median overall survival of patients with CXCR4-positive tumors was 20 months and with CXCR4-negative tumors, 76 months (difference = 56 months, 95% confidence interval [CI] = 4 to 108 months; P<.001). The median disease-specific survival of patients with CXCR4-positive tumors was 25 months and with CXCR4-negative tumors was 97 months (difference = 72 months, 95% CI = 34 to 110 months; P<.001). CXCR4 expression was statistically significantly associated with increased lymph node microinvolvement (P<.001) and with increased bone marrow micrometastasis (P<.001). In multivariable analysis, CXCR4 expression, compared with its nonexpression, was identified as the independent variable that was most strongly associated with reduced disease-specific survival (relative risk [RR] of death = 2.03, 95% CI = 1.20 to 3.41; P = .008) and overall survival (RR of death = 2.18, 95% CI = 1.33 to 3.59; P = .002). Conclusion: CXCR4 expression was associated with poor clinical outcome in esophageal cancer patients. CXCR4 may have a role in early metastatic spread because its expression was associated with micrometastases to both the lymph nodes and bone marrow. Thus, CXCR4 should be explored further as a target for adjuvant therapy for micrometastatic disease.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Alix-Panabieres, S. Riethdorf, and K. Pantel Circulating Tumor Cells and Bone Marrow Micrometastasis Clin. Cancer Res., August 15, 2008; 14(16): 5013 - 5021. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Diomedi-Camassei, H. P. McDowell, M. A. De Ioris, S. Uccini, P. Altavista, G. Raschella, R. Vitali, O. Mannarino, L. De Sio, D. A. Cozzi, et al. Clinical Significance of CXC Chemokine Receptor-4 and c-Met in Childhood Rhabdomyosarcoma Clin. Cancer Res., July 1, 2008; 14(13): 4119 - 4127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J Yeung and H Chang Genomic aberrations and immunohistochemical markers as prognostic indicators in multiple myeloma J. Clin. Pathol., July 1, 2008; 61(7): 832 - 836. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Meijer, J. Ogink, B. Kreike, D. Nuyten, K. E. de Visser, and E. Roos The Chemokine Receptor CXCR6 and Its Ligand CXCL16 Are Expressed in Carcinomas and Inhibit Proliferation Cancer Res., June 15, 2008; 68(12): 4701 - 4708. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A Vincent-Salomon, F C Bidard, and J Y Pierga Bone marrow micrometastasis in breast cancer: review of detection methods, prognostic impact and biological issues J. Clin. Pathol., May 1, 2008; 61(5): 570 - 576. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Pantel, C. Alix-Panabieres, and S. Riethdorf Circulating Tumor Cells: Detection and Clinical Relevance Am. Assoc. Cancer Res. Educ. Book, April 12, 2008; 2008(1): 603 - 610. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Wels, R. N. Kaplan, S. Rafii, and D. Lyden Migratory neighbors and distant invaders: tumor-associated niche cells Genes & Dev., March 1, 2008; 22(5): 559 - 574. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Rafii, B. Psaila, J. Butler, D. K. Jin, and D. Lyden Regulation of Vasculogenesis by Platelet-Mediated Recruitment of Bone Marrow-Derived Cells Arterioscler. Thromb. Vasc. Biol., February 1, 2008; 28(2): 217 - 222. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ishigami, S. Natsugoe, H. Okumura, M. Matsumoto, A. Nakajo, Y. Uenosono, T. Arigami, Y. Uchikado, T. Setoyama, H. Arima, et al. Clinical Implication of CXCL12 Expression in Gastric Cancer Ann. Surg. Oncol., November 1, 2007; 14(11): 3154 - 3158. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Uchida, T. Onoue, Y. Tomizuka, N. M. Begum, Y. Miwa, H. Yoshida, and M. Sato Involvement of an Autocrine Stromal Cell Derived Factor-1/CXCR4 System on the Distant Metastasis of Human Oral Squamous Cell Carcinoma Mol. Cancer Res., July 1, 2007; 5(7): 685 - 694. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J Kodama, Hasengaowa, T Kusumoto, N Seki, T Matsuo, Y Ojima, K Nakamura, A Hongo, and Y Hiramatsu Association of CXCR4 and CCR7 chemokine receptor expression and lymph node metastasis in human cervical cancer Ann. Onc., January 1, 2007; 18(1): 70 - 76. [Abstract] [Full Text] [PDF]
|
|