title: Molecular apocrine differentiation is a common feature of breast cancer in patients with germline PTEN mutations.
abstract: BACKGROUND
  Breast carcinoma is the main malignant tumor occurring in patients with Cowden disease, a cancer-prone syndrome caused by germline mutation of the tumor suppressor gene PTEN characterized by the occurrence throughout life of hyperplastic, hamartomatous and malignant growths affecting various organs. The absence of known histological features for breast cancer arising in a PTEN-mutant background prompted us to explore them for potential new markers.
  
  
  METHODS
  We first performed a microarray study of three tumors from patients with Cowden disease in the context of a transcriptomic study of 74 familial breast cancers. A subsequent histological and immunohistochemical study including 12 additional cases of Cowden disease breast carcinomas was performed to confirm the microarray data.
  
  
  RESULTS
  Unsupervised clustering of the 74 familial tumors followed the intrinsic gene classification of breast cancer except for a group of five tumors that included the three Cowden tumors. The gene expression profile of the Cowden tumors shows considerable overlap with that of a breast cancer subgroup known as molecular apocrine breast carcinoma, which is suspected to have increased androgenic signaling and shows frequent ERBB2 amplification in sporadic tumors. The histological and immunohistochemical study showed that several cases had apocrine histological features and expressed GGT1, which is a potential new marker for apocrine breast carcinoma.
  
  
  CONCLUSIONS
  These data suggest that activation of the ERBB2-PI3K-AKT pathway by loss of PTEN at early stages of tumorigenesis promotes the formation of breast tumors with apocrine features.
authors: INSERM U916, Université de Bordeaux, Institut Bergonié, 229 cours de l'Argonne, 33000, Bordeaux, France.
authors: Guillaume
authors: G
authors: Banneau
authors: Mickaël
authors: M
authors: Guedj
authors: Gaëtan
authors: G
authors: MacGrogan
authors: Isabelle
authors: I
authors: de Mascarel
authors: Valerie
authors: V
authors: Velasco
authors: Renaud
authors: R
authors: Schiappa
authors: Valerie
authors: V
authors: Bonadona
authors: Albert
authors: A
authors: David
authors: Catherine
authors: C
authors: Dugast
authors: Brigitte
authors: B
authors: Gilbert-Dussardier
authors: Olivier
authors: O
authors: Ingster
authors: Pierre
authors: P
authors: Vabres
authors: Frederic
authors: F
authors: Caux
authors: Aurelien
authors: A
authors: de Reynies
authors: Richard
authors: R
authors: Iggo
authors: Nicolas
authors: N
authors: Sevenet
authors: Françoise
authors: F
authors: Bonnet
authors: Michel
authors: M
authors: Longy
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D058534:Class I Phosphatidylinositol 3-Kinases; D016000:Cluster Analysis; D055028:Comparative Genomic Hybridization; D020869:Gene Expression Profiling; D018095:Germ-Line Mutation; D006223:Hamartoma Syndrome, Multiple / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D020411:Oligonucleotide Array Sequence Analysis; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D025341:Principal Component Analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D005723:gamma-Glutamyltransferase; C484760:PIK3CA protein, human; C508053:ERBB2 protein, human; C494929:PTEN protein, human