Abstract
BackgroundCXCL12 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.MethodsImmunohistochemistry 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.ResultsEpithelial 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.ConclusionOur 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.Trial RegistrationClinicalTrials.gov: NCT00052468
Highlights
CXCL12 has been widely reported to play a biologically relevant role in tumor growth and spread
Detection of CXCL12 products in healthy and malignant ovarian epithelial cells The cellular expression of CXCL12 was examined by IHC on sections isolated from five healthy ovaries, eight serous or mucinous benign tumors, eight serous or mucinous borderline epithelial tumors, three non epithelial ovarian tumors (i.e. 2 granulosa tumors and 1 dysgerminoma), and 183 invasive epithelial ovarian cancer (EOC)
Epithelial cells isolated from malignant ascites and identified as CD326+ cells were stained for CXCL12, whereas their CD326- non epithelial counterparts, consisting mostly of CD45+ leukocytes, were not stained for CXCL12 (Figure 1E)
Summary
CXCL12 has been widely reported to play a biologically relevant role in tumor growth and spread. This aspect has recently been addressed with the identification of several biomarkers for the identification of histologic subtypes and the more accurate prediction of patient outcome [4,5,6,7,8,9] Chemokines and their receptors have been known for many years to influence the development of primary epithelial tumors, in which they regulate the proliferation and survival of tumor cells, tumor-infiltrating leukocytes, angiogenesis and metastasis [10,11,12]. In epithelial cancers, these molecules play a key role in controlling both autocrine and paracrine communication between the different cell types of the tumor microenvironment [13]. Chemokines and their receptors may constitute new biomarkers of potential prognostic value in various cancers, including EOC
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
