MARCKS protein overexpression in inflammatory breast cancer
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Maroua Manai1,5,6,7, Jeanne Thomassin-Piana2,*, Amor Gamoudi6,*, Pascal Finetti1,*, Marc Lopez1, Radhia Eghozzi6, Sinda Ayadi6, Olfa Ben Lamine6, Mohamed Manai5, Khaled Rahal6, Emmanuelle Charafe-Jauffret2,3, Jocelyne Jacquemier2, Patrice Viens3,4, Daniel Birnbaum1, Hamouda Boussen5,7, Max Chaffanet1, François Bertucci1,3,4
1Département d’Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Aix Marseille Université, Marseille, France
2Département de Bio-Pathologie, Institut Paoli-Calmettes, Marseille, France
3UFR de Médecine, Aix Marseille Université, Marseille, France
4Département d’Oncologie Médicale, Institut Paoli-Calmettes, Marseille, France
5Département de Biologie, Unité de Biochimie et Biologie Moléculaire, Faculté des Sciences de Tunis, Université de Tunis El Manar, Tunisie
6Département d’Oncologie Médicale, Institut Salah Azaiez, Tunis, Tunisie
7Service d’Oncologie Médicale, Hôpital l’Ariana, Tunis, Tunisie
*These authors contributed equally to second authors
François Bertucci, email: firstname.lastname@example.org
Keywords: expression, immunohistochemistry, inflammatory breast cancer, MARCKS, survival
Received: July 29, 2016 Accepted: December 14, 2016 Published: December 21, 2016
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.
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