title: Expression of CXCR4 indicates poor prognosis in patients with clear cell carcinoma of the ovary.
abstract: Recent reports have shown that CXCR4 is expressed in various solid tumors and is involved in tumor development and metastasis. We examined the distribution and expression of this molecule in clear cell carcinoma of the ovary to elucidate its clinical significance. Paraffin sections from clear cell carcinoma of the ovary tissues (n = 42) were immunostained with CXCR4 antibody, and the staining intensities were evaluated. The clinicopathologic factors examined were age, FIGO (International Federation of Gynecology and Obstetrics) staging, preoperative value of cancer antigen 125 test, and residual tumor after cytoreductive surgery. Overall survival and progression-free survival were evaluated using the Kaplan-Meier method, and multivariate analysis was completed using Cox proportional hazards analysis. Of the 42 carcinomas, lower level CXCR4 immunoexpression was observed in 21 cases (50.0%) (CXCR4(low) group); and higher level immunoexpression, in 21 cases (50.0%) (CXCR4(high) group). Five-year overall survival was significantly poorer in the CXCR4(high) group than in the CXCR4(low) group (overall survival, CXCR4(low) group [90.2%], CXCR4(high) group [50.3%]; P = .0002). In addition, CXCR4(high) immunoexpression significantly predicted a poorer progression-free survival when compared with lower expression (5-year progression-free survival, CXCR4(low) group [90.5%], CXCR4(high) group [36.2%]; P < .0001). Furthermore, multivariate analyses including the age, preoperative cancer antigen 125 test value, FIGO stage, and CXCR4 expressions revealed that CXCR4(high) expression was an independent prognostic factor for poorer overall survival and progression-free survival of patients with clear cell carcinoma of the ovary (overall survival, P = .0011; progression-free survival, P = .0008, respectively). Our current study suggested that the assessment of CXCR4 immunoreactivity may be a useful prognostic indicator and that CXCR4 may play a critical role in the progression of clear cell carcinoma of the ovary.
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine Tsuruma-cho 65, Showa-ku, Nagoya, Japan.
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Sekiya
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kajiyama
authors.forename: Kotaro
authors.initials: K
authors.lastname: Sakai
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Umezu
authors.forename: Mika
authors.initials: M
authors.lastname: Mizuno
authors.forename: Kiyosumi
authors.initials: K
authors.lastname: Shibata
authors.forename: Eiko
authors.initials: E
authors.lastname: Yamamoto
authors.forename: Sawako
authors.initials: S
authors.lastname: Fujiwara
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Nagasaka
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Kikkawa
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D019718:Receptors, CXCR4 / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; C527276:CXCR4 protein, human; D019718:Receptors, CXCR4