title: MARCKS protein overexpression in inflammatory breast cancer.
abstract: 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.
  
  
  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.
authors.affiliation: Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Aix Marseille Université, Marseille, France.|Département de Biologie, Unité de Biochimie et Biologie Moléculaire, Faculté des Sciences de Tunis, Université de Tunis El Manar, Tunisie.|Département d'Oncologie Médicale, Institut Salah Azaiez, Tunis, Tunisie.|Service d'Oncologie Médicale, Hôpital l'Ariana, Tunis, Tunisie.
authors.forename: Maroua
authors.initials: M
authors.lastname: Manai
authors.affiliation: Département de Bio-Pathologie, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Thomassin-Piana
authors.affiliation: Département d'Oncologie Médicale, Institut Salah Azaiez, Tunis, Tunisie.
authors.forename: Amor
authors.initials: A
authors.lastname: Gamoudi
authors.affiliation: Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Aix Marseille Université, Marseille, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Finetti
authors.affiliation: Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Aix Marseille Université, Marseille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Lopez
authors.affiliation: Département d'Oncologie Médicale, Institut Salah Azaiez, Tunis, Tunisie.
authors.forename: Radhia
authors.initials: R
authors.lastname: Eghozzi
authors.affiliation: Département d'Oncologie Médicale, Institut Salah Azaiez, Tunis, Tunisie.
authors.forename: Sinda
authors.initials: S
authors.lastname: Ayadi
authors.affiliation: Département d'Oncologie Médicale, Institut Salah Azaiez, Tunis, Tunisie.
authors.forename: Olfa Ben
authors.initials: OB
authors.lastname: Lamine
authors.affiliation: Département de Biologie, Unité de Biochimie et Biologie Moléculaire, Faculté des Sciences de Tunis, Université de Tunis El Manar, Tunisie.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Manai
authors.affiliation: Département d'Oncologie Médicale, Institut Salah Azaiez, Tunis, Tunisie.
authors.forename: Khaled
authors.initials: K
authors.lastname: Rahal
authors.affiliation: Département de Bio-Pathologie, Institut Paoli-Calmettes, Marseille, France.|UFR de Médecine, Aix Marseille Université, Marseille, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Charafe-Jauffret
authors.affiliation: Département de Bio-Pathologie, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Jacquemier
authors.affiliation: UFR de Médecine, Aix Marseille Université, Marseille, France.|Département d'Oncologie Médicale, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Viens
authors.affiliation: Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Aix Marseille Université, Marseille, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Birnbaum
authors.affiliation: Département de Biologie, Unité de Biochimie et Biologie Moléculaire, Faculté des Sciences de Tunis, Université de Tunis El Manar, Tunisie.|Service d'Oncologie Médicale, Hôpital l'Ariana, Tunis, Tunisie.
authors.forename: Hamouda
authors.initials: H
authors.lastname: Boussen
authors.affiliation: Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Aix Marseille Université, Marseille, France.
authors.forename: Max
authors.initials: M
authors.lastname: Chaffanet
authors.affiliation: Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Aix Marseille Université, Marseille, France.|UFR de Médecine, Aix Marseille Université, Marseille, France.|Département d'Oncologie Médicale, Institut Paoli-Calmettes, Marseille, France.
authors.forename: François
authors.initials: F
authors.lastname: Bertucci
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D005602:France; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D058922:Inflammatory Breast Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D000076250:Myristoylated Alanine-Rich C Kinase Substrate / Q000032:analysis* / Q000235:genetics; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014416:Tunisia; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C000619710:MARCKS protein, human; D012333:RNA, Messenger; D000076250:Myristoylated Alanine-Rich C Kinase Substrate
keywords: MARCKS; expression; immunohistochemistry; inflammatory breast cancer; survival