High PTPN13 expression in high grade serous ovarian carcinoma is associated with a better patient outcome
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Véronique D’Hondt1,2, Magalie Lacroix-Triki3, Marta Jarlier4, Florence Boissiere-Michot5, Carole Puech1,2,6,7, Peter Coopman1,2,6,7, Dionyssios Katsaros8 and Gilles Freiss1,2,6,7
1IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier F-34298, France
2Institut régional du Cancer de Montpellier, Montpellier F-34298, France
3Département de Biologie et Pathologie Médicales, Gustave-Roussy Cancer Campus, 94805 Villejuif cedex, France
4Unité de Biométrie, Institut régional du Cancer de Montpellier, Montpellier F-34298, France
5Unité de Recherche Translationnelle, Institut Régional du Cancer de Montpellier, Montpellier F-34298, France
6INSERM, U 1194, Montpellier F-34298, France
7Université de Montpellier, Montpellier F-34090, France
8Azienda Ospedaliero-Universitaria Cittadella Salute, Presidio S. Anna and Department of Surgical Science, Gynecology, University of Torino, Torino, Italy
Gilles Freiss, email: [email protected]
Keywords: high-grade serous ovarian carcinoma; PTPN13; 4q LOH; tyrosine phosphatase; prognosis
Received: May 16, 2017 Accepted: August 16, 2017 Published: September 21, 2017
Background: Chromosome 4q loss of heterozygosity (LOH) is frequently observed in high-grade serous ovarian carcinoma (HGSOC). However, this LOH has not been clearly associated with the inactivation of any tumor suppressor gene(s). As the tumor suppressor gene PTPN13 is located on chromosome 4q21, we investigated its expression in HGSOC.
Methods: PTPN13 protein expression was investigated by immunohistochemistry (IHC) in normal ovary epithelium and in 30 HGSOC samples, whereas PTPN13 mRNA expression was quantified by RT-PCR in another independent cohort of 28 HGSOC samples. Patients in both cohorts were followed for more than 8.5 years.
Results: PTPN13 protein expression was lower in one third of HGSOC samples compared with normal ovary epithelium. In both cohorts, high PTPN13 expression level (mRNA or protein) in the tumor was associated with favorable outcome and significantly longer survival (HR=0.27; p=0.0087 and HR=0.42; p=0.03, respectively).
Conclusion: This study demonstrates, for the first time, that high PTPN13 expression level is a prognostic indicator of favorable outcome in patients with HGSOC. This finding, in conjunction with our previous mechanistic studies, suggests that PTPN13 loss, possibly by 4q LOH, enhances HGSOC aggressiveness and highlight the interest of studying PTPN13 signaling in HGSOC to identify new potential therapeutic targets.
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