title: CXCL12 expression by healthy and malignant ovarian epithelial cells.
abstract: BACKGROUND
  CXCL12 has been widely reported to play a biologically relevant role in tumor growth and spread. In epithelial ovarian cancer (EOC), CXCL12 enhances tumor angiogenesis and contributes to the immunosuppressive network. However, its prognostic significance remains unclear. We thus compared CXCL12 status in healthy and malignant ovaries, to assess its prognostic value.
  
  
  METHODS
  Immunohistochemistry was used to analyze CXCL12 expression in the reproductive tracts, including the ovaries and fallopian tubes, of healthy women, in benign and borderline epithelial tumors, and in a series of 183 tumor specimens from patients with advanced primary EOC enrolled in a multicenter prospective clinical trial of paclitaxel/carboplatin/gemcitabine-based chemotherapy (GINECO study). Univariate COX model analysis was performed to assess the prognostic value of clinical and biological variables. Kaplan-Meier methods were used to generate progression-free and overall survival curves.
  
  
  RESULTS
  Epithelial cells from the surface of the ovary and the fallopian tubes stained positive for CXCL12, whereas the follicles within the ovary did not. Epithelial cells in benign, borderline and malignant tumors also expressed CXCL12. In EOC specimens, CXCL12 immunoreactivity was observed mostly in epithelial tumor cells. The intensity of the signal obtained ranged from strong in 86 cases (47%) to absent in 18 cases (<10%). This uneven distribution of CXCL12 did not reflect the morphological heterogeneity of EOC. CXCL12 expression levels were not correlated with any of the clinical parameters currently used to determine EOC prognosis or with HER2 status. They also had no impact on progression-free or overall survival.
  
  
  CONCLUSIONS
  Our findings highlight the previously unappreciated constitutive expression of CXCL12 on healthy epithelia of the ovary surface and fallopian tubes, indicating that EOC may originate from either of these epithelia. We reveal that CXCL12 production by malignant epithelial cells precedes tumorigenesis and we confirm in a large cohort of patients with advanced EOC that CXCL12 expression level in EOC is not a valuable prognostic factor in itself.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT00052468.
authors.affiliation: INSERM UMR_S 996, Université Paris-Sud 11, Clamart, France. veronique.machelon@u-psud.fr
authors.forename: Véronique
authors.initials: V
authors.lastname: Machelon
authors.forename: Françoise
authors.initials: F
authors.lastname: Gaudin
authors.forename: Sophie
authors.initials: S
authors.lastname: Camilleri-Broët
authors.forename: Salam
authors.initials: S
authors.lastname: Nasreddine
authors.forename: Laurence
authors.initials: L
authors.lastname: Bouchet-Delbos
authors.forename: Eric
authors.initials: E
authors.lastname: Pujade-Lauraine
authors.forename: Jerôme
authors.initials: J
authors.lastname: Alexandre
authors.forename: Laurence
authors.initials: L
authors.lastname: Gladieff
authors.forename: Fernando
authors.initials: F
authors.lastname: Arenzana-Seisdedos
authors.forename: Dominique
authors.initials: D
authors.lastname: Emilie
authors.forename: Sophie
authors.initials: S
authors.lastname: Prévot
authors.forename: Philippe
authors.initials: P
authors.lastname: Broët
authors.forename: Karl
authors.initials: K
authors.lastname: Balabanian
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D000077216:Carcinoma, Ovarian Epithelial; D054377:Chemokine CXCL12 / Q000378:metabolism*; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data; D015331:Cohort Studies; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006262:Health; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D010053:Ovary / Q000378:metabolism* / Q000473:pathology; D011237:Predictive Value of Tests; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data
chemical_list: D014408:Biomarkers, Tumor; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12