title: Phosphatidylinositol-3-kinase pathway mutations are common in breast columnar cell lesions.
abstract: The phosphatidylinositol-3-kinase pathway is one of the most commonly mutated pathways in invasive breast carcinoma, with PIK3CA mutations in ∼25% of invasive carcinomas, and AKT1 mutations in up to 5%. Ductal carcinoma in situ, and benign papillomas harbor similar mutations. However, activating point mutations in breast columnar cell lesions have been infrequently studied. Twenty-three breast resection specimens containing columnar cell lesions were identified; 14 with associated invasive carcinoma or carcinoma in situ. DNA extracts were prepared from formalin-fixed paraffin-embedded tissue and screened for a panel of point mutations (321 mutations in 30 genes) using a multiplex PCR panel with mass-spectroscopy readout. PIK3CA mutations were identified in 13/24 columnar cell lesions (54%) and 3/8 invasive carcinomas (37%). The mutation status of columnar cell lesions and associated carcinoma was frequently discordant. Of the 14 cases, only 5 demonstrated the same genotype in matched samples of columnar cell lesions and carcinoma (4 wild type, 1 PIK3CA H1047R). Interestingly, five patients had mutations in columnar cell lesions with wild-type carcinoma; two patients had different point mutations in columnar cell lesions and carcinoma. Only three cases had wild-type columnar cell lesion and mutated carcinoma. The 50% PIK3CA mutation prevalence in columnar cell lesions is greater than reported in most studies of invasive breast cancer. Further, columnar cell lesions and carcinoma were frequently discordant for PIK3CA/AKT1 mutation status. These findings raise interesting questions about the role of PIK3CA/AKT pathway in breast carcinogenesis, and the biologic/precursor potential of columnar cell lesions.
authors.affiliation: Department of Pathology and Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA. troxellm@ohsu.edu
authors.forename: Megan L
authors.initials: ML
authors.lastname: Troxell
authors.forename: Alayne L
authors.initials: AL
authors.lastname: Brunner
authors.forename: Tanaya
authors.initials: T
authors.lastname: Neff
authors.forename: Andrea
authors.initials: A
authors.lastname: Warrick
authors.forename: Carol
authors.initials: C
authors.lastname: Beadling
authors.forename: Kelli
authors.initials: K
authors.lastname: Montgomery
authors.forename: Shirley
authors.initials: S
authors.lastname: Zhu
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Corless
authors.forename: Robert B
authors.initials: RB
authors.lastname: West
mesh_terms: D001941:Breast Diseases / Q000150:complications* / Q000201:enzymology / Q000235:genetics*; D001943:Breast Neoplasms / Q000150:complications* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000150:complications / Q000201:enzymology / Q000235:genetics; D005260:Female; D006801:Humans; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D019869:Phosphatidylinositol 3-Kinases