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

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Doghri, Raoudha | Manai, Maroua | Finetti, Pascal | Driss, Maha | Agavnian, Emilie | Lopez, Marc | Elghardallou, Meriam | Charafe-Jauffret, Emmanuelle | Manai, Mohamed | Chaffanet, Max | Birnbaum, Daniel | Mrad, Karima | Bertucci, Francois

Edité par CCSD ; MDPI -

International audience. 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 x 10(-3)). By contrast, stromal MARCKS expression was more frequent in tumor samples (77%) than in normal samples (22%; p = 1.41 x 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.

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