title: Chemokine receptor CXCR4 expression is correlated with VEGF expression and poor survival in soft-tissue sarcoma.
abstract: The expression of chemokine receptor CXCR4 has been associated with poor prognosis and VEGF expression in several kinds of human malignancy. We measured CXCR4 expression levels in soft-tissue sarcoma and compared them with VEGF expression or microvessel density (MVD). We used real-time quantitative PCR to examine the CXCR4 and VEGF expression levels in a total 176 tumors, including 24 intermediate tumors, 24 malignant round-cell tumors (MRCTs) and 128 malignant non-round-cell tumors (MNRCTs). We also assessed their immunohistochemical expression of CXCR4 and VEGF, MVD and proliferative activities, as measured by the MIB-1-labeling index (LI). Furthermore, we evaluated their significance with respect to patient survival rates in MNRCTs, using the Cox regression model. Within the different types of tumor tissue, the expression levels of CXCR4 (p < 0.0001) and VEGF (p < 0.0001) in MNRCTs were significantly higher than those in intermediate tumors or MRCTs. Immunohistochemical expression levels of CXCR4 and VEGF were significantly correlated with their mRNA expression levels (p < 0.0001). Significant positive correlation was found between CXCR4 and VEGF expression in 112 primary MNRCTs (r = 0.434, p < 0.0001). Moreover, both univariate (p < 0.0001) and Cox multivariate analysis (p = 0.0001) revealed that overexpression of CXCR4 was an independent adverse prognostic factor, in addition to high stage according to the American Joint Committee on Cancer and a high MIB-1-LI. Determination of the CXCR4 expression level as a novel marker can provide useful prognostic information for patients and it could be a candidate for molecular targeting therapy in MNRCTs of soft-tissue sarcomas.
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. oda@surgpath.med.kyushu-u.ac.jp
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
authors.forename: Naomi
authors.initials: N
authors.lastname: Tateishi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matono
authors.forename: Suguru
authors.initials: S
authors.lastname: Matsuura
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Yamamaoto
authors.forename: Sadafumi
authors.initials: S
authors.lastname: Tamiya
authors.forename: Ryohei
authors.initials: R
authors.lastname: Yokoyama
authors.forename: Shuichi
authors.initials: S
authors.lastname: Matsuda
authors.forename: Yukihide
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: Masazumi
authors.initials: M
authors.lastname: Tsuneyoshi
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D002470:Cell Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008833:Microcirculation; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000096:biosynthesis*; D012509:Sarcoma / Q000378:metabolism* / Q000401:mortality*; D012983:Soft Tissue Neoplasms / Q000378:metabolism* / Q000401:mortality*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; C527276:CXCR4 protein, human; D019718:Receptors, CXCR4; D042461:Vascular Endothelial Growth Factor A