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Tumor-cell homing to lymph nodes and bone marrow and CXCR4 expression in esophageal cancer.
J Natl Cancer Inst. 2005 Dec 21; 97(24):1840-7.JNCI

Abstract

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.

Authors+Show Affiliations

Klinik fuer Allgemein-, Viszeral- und Thoraxchirurgie, Universitaetsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. jkaifi@uke.uni-hamburg.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16368946

Citation

Kaifi, Jussuf T., et al. "Tumor-cell Homing to Lymph Nodes and Bone Marrow and CXCR4 Expression in Esophageal Cancer." Journal of the National Cancer Institute, vol. 97, no. 24, 2005, pp. 1840-7.
Kaifi JT, Yekebas EF, Schurr P, et al. Tumor-cell homing to lymph nodes and bone marrow and CXCR4 expression in esophageal cancer. J Natl Cancer Inst. 2005;97(24):1840-7.
Kaifi, J. T., Yekebas, E. F., Schurr, P., Obonyo, D., Wachowiak, R., Busch, P., Heinecke, A., Pantel, K., & Izbicki, J. R. (2005). Tumor-cell homing to lymph nodes and bone marrow and CXCR4 expression in esophageal cancer. Journal of the National Cancer Institute, 97(24), 1840-7.
Kaifi JT, et al. Tumor-cell Homing to Lymph Nodes and Bone Marrow and CXCR4 Expression in Esophageal Cancer. J Natl Cancer Inst. 2005 Dec 21;97(24):1840-7. PubMed PMID: 16368946.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tumor-cell homing to lymph nodes and bone marrow and CXCR4 expression in esophageal cancer. AU - Kaifi,Jussuf T, AU - Yekebas,Emre F, AU - Schurr,Paulus, AU - Obonyo,Dennis, AU - Wachowiak,Robin, AU - Busch,Philipp, AU - Heinecke,Antje, AU - Pantel,Klaus, AU - Izbicki,Jakob R, PY - 2005/12/22/pubmed PY - 2005/12/28/medline PY - 2005/12/22/entrez SP - 1840 EP - 7 JF - Journal of the National Cancer Institute JO - J Natl Cancer Inst VL - 97 IS - 24 N2 - 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. SN - 1460-2105 UR - https://www.unboundmedicine.com/medline/citation/16368946/Tumor_cell_homing_to_lymph_nodes_and_bone_marrow_and_CXCR4_expression_in_esophageal_cancer_ L2 - https://academic.oup.com/jnci/article-lookup/doi/10.1093/jnci/dji431 DB - PRIME DP - Unbound Medicine ER -