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Open Access Highly Accessed Research article

CXCL12 expression by healthy and malignant ovarian epithelial cells

Véronique Machelon1*, Françoise Gaudin1, Sophie Camilleri-Broët23, Salam Nasreddine1, Laurence Bouchet-Delbos1, Eric Pujade-Lauraine4, Jerôme Alexandre4, Laurence Gladieff5, Fernando Arenzana-Seisdedos6, Dominique Emilie17, Sophie Prévot8, Philippe Broët2 and Karl Balabanian1*

Author Affiliations

1 INSERM UMR_S 996, Université Paris-Sud 11, Clamart, 92140 France

2 JE2492, Assistance-Publique Hôpitaux de Paris (AP-HP), Université Paris-Sud 11, Villejuif, 94800 France

3 Cabinet de Pathologie Tolbiac, Paris, 75013 France

4 Service d'Oncologie médicale, AP-HP, Université Paris Descartes, Hôpital Hôtel-Dieu, Paris, 75001 France

5 Centre Claudius Regaud, Toulouse, 33000 France

6 INSERM U819, Laboratoire de Pathogénie Virale, Institut Pasteur, Paris, 75015 France

7 Service de Microbiologie-Immunologie Biologique, AP-HP, Université Paris-Sud 11, Hôpital Antoine-Béclère, Clamart, 92140 France

8 Service d'Anatomie et de Cytologie Pathologiques, AP-HP, Université Paris-Sud 11, Hôpital Antoine-Béclère, Clamart, 92140 France

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BMC Cancer 2011, 11:97  doi:10.1186/1471-2407-11-97

Published: 16 March 2011

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.

Conclusion

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.

Trial Registration

ClinicalTrials.gov: NCT00052468