MARCKS protein overexpression in inflammatory breast cancer

Maroua Manai (1) , Jeanne Thomassin-Piana (1) , Amor Gamoudi (2) , Pascal Finetti (1) , Marc Lopez (1) , Radhia Eghozzi (3) , Sinda Ayadi (3) , Olfa Ben Lamine (3) , Mohamed Manai (4) , Khaled Rahal (3) , Emmanuelle Charafe-Jauffret (1) , Jocelyne Jacquemier (5) , Patrice Viens (1) , Daniel Birnbaum (1) , Hamouda Boussen (6, 7) , Max Chaffanet (1) , François Bertucci (1)

1 CRCM - Centre de Recherche en Cancérologie de Marseille
2 Inst Carcinol Salah Azaiz Tunis
3 Institut Salah Azaiez de Cancer
4 UTM - Université de Tunis El Manar
5 Département de Biopathologie [Marseille]
6 Unité de Biochimie et Biologie Moléculaire [Tunis, Tunisie]
7 Service d’Oncologie Médicale [Tunis, Tunisie]

Background: Inflammatory breast cancer (IBC) is the most aggressive form of locally-advanced breast cancer. Identification of new therapeutic targets is crucial. We previously reported MARCKS mRNA overexpression in IBC in the largest transcriptomics study reported to date. Here, we compared MARCKS protein expression in IBC and non-IBC samples, and searched for correlations between protein expression and clinicopathological features. Results: Tumor samples showed heterogeneity with respect to MARCKS staining: 18% were scored as MARCKS-positive (stained cells ≥ 1%) and 82% as MARCKS-negative. MARCKS expression was more frequent in IBC (36%) than in non-IBC (11%; p = 1.4E−09), independently from molecular subtypes and other clinicopathological variables. We found a positive correlation between protein and mRNA expression in the 148/502 samples previously analyzed for MARCKS mRNA expression. MARCKS protein expression was associated with other poor-prognosis features in the whole series of samples such as clinical axillary lymph node or metastatic extension, high pathological grade, ER-negativity, PR-negativity, HER2-positivity, and triple-negative and HER2+ statutes. In IBC, MARCKS expression was the sole tested variable associated with poor MFS. Materials and Methods: We retrospectively analyzed MARCKS protein expression by immunohistochemistry in 502 tumors, including 133 IBC and 369 non-IBC, from Tunisian and French patients. All samples were pre-therapeutic clinical samples. We searched for correlations between MARCKS expression and clinicopathological features including the IBC versus non-IBC phenotype and metastasis-free survival (MFS). Conclusions: MARCKS overexpression might in part explain the poor prognosis of IBC. As an oncogene associated with poor MFS, MARCKS might represent a new potential therapeutic target in IBC.

Mots clés: MARCKS; inflammatory breast cancer; survival; expression; immunohistochemistry

Domaines: Sciences du Vivant [q-bio]; Cancer

Maroua Manai, Jeanne Thomassin-Piana, Amor Gamoudi, Pascal Finetti, Marc Lopez, et al.. MARCKS protein overexpression in inflammatory breast cancer. Oncotarget, 2017, 8, pp.6246 - 6257. ⟨10.18632/oncotarget.14057⟩. ⟨hal-01787705⟩