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Int. J. Mol. Sci. 2018, 19(1), 41; https://doi.org/10.3390/ijms19010041

Stromal Expression of MARCKS Protein in Ovarian Carcinomas Has Unfavorable Prognostic Value

1
Département d’Anatomie Pathologique, Institut Salah Azaiez, Bab Saadoun, Tunis 1006, Tunisia
2
Département d’Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, INSERM UMR1068, CNRS UMR7258, Aix-Marseille Université, 13007 Marseille, France
3
Département de Biologie, Unité de Biochimie et Biologie Moléculaire, Faculté des Sciences de Tunis, Université de Tunis El Manar, Tunis 1068, Tunisia
4
Département de Bio-Pathologie, Institut Paoli-Calmettes, 13009 Marseille, France
5
Département de Médicine Communautaire, Faculté de Médecine de Sousse, Sousse 4000, Tunisia
6
UFR de Médecine, Aix Marseille Université, 13007 Marseille, France
7
Département d’Oncologie Médicale, Institut Paoli-Calmettes, 13009 Marseille, France
These authors contributed equally and should be considered as first co-authors.
*
Author to whom correspondence should be addressed.
Received: 21 November 2017 / Revised: 13 December 2017 / Accepted: 21 December 2017 / Published: 23 December 2017
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Abstract

Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. Identification of new therapeutic targets is crucial. MARCKS, myristoylated alanine-rich C-kinase substrate, has been implicated in aggressiveness of several cancers and MARCKS inhibitors are in development. Using immunohistochemistry (IHC), we retrospectively assessed MARCKS expression in epithelial and stromal cells of 118 pre-chemotherapy EOC samples and 40 normal ovarian samples from patients treated at Salah Azaiez Institute. We compared MARCKS expression in normal versus cancer samples, and searched for correlations with clinicopathological features, including overall survival (OS). Seventy-five percent of normal samples showed positive epithelial MARCKS staining versus 50% of tumor samples (p = 6.02 × 10−3). By contrast, stromal MARCKS expression was more frequent in tumor samples (77%) than in normal samples (22%; p = 1.41 × 10−9). There was no correlation between epithelial and stromal IHC MARCKS statutes and prognostic clinicopathological features. Stromal MARCKS expression was correlated with shorter poor OS in uni- and multivariate analyses. Stromal MARCKS overexpression in tumors might contribute to cancer-associated fibroblasts activation and to the poor prognosis of EOC, suggesting a potential therapeutic interest of MARCKS inhibition for targeting the cooperative tumor stroma. View Full-Text
Keywords: epithelial ovarian cancer; immunohistochemistry; MARCKS; prognosis; stroma; survival epithelial ovarian cancer; immunohistochemistry; MARCKS; prognosis; stroma; survival
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Doghri, R.; Manai, M.; Finetti, P.; Driss, M.; Agavnian, E.; Lopez, M.; Elghardallou, M.; Charafe-Jauffret, E.; Manai, M.; Chaffanet, M.; Birnbaum, D.; Mrad, K.; Bertucci, F. Stromal Expression of MARCKS Protein in Ovarian Carcinomas Has Unfavorable Prognostic Value. Int. J. Mol. Sci. 2018, 19, 41.

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