title: PIK3CAandAKT1mutations in hidradenoma papilliferum.
abstract: OBJECTIVE
  Hidradenoma papilliferum (HP) is a benign vulvar neoplasm that arises from anogenital mammary-like glands, and its morphology is similar to mammary intraductal papilloma. The aim of this study was to investigate oncogenic mutations involved in the tumourigenesis of HP. We focused specifically onPIK3CAandAKT1mutations, which are both reported to be detected in 33% of mammary intraductal papillomas.
  
  
  METHODS
  In total, seven HP cases were analysed. Clinicopathological analyses and immunohistochemistry for oestrogen receptor, p63, smooth muscle actin (SMA), p53 and β-catenin were performed. Furthermore,PIK3CA,AKT1, BRAFandKRAShot spot mutations were examined by Sanger sequencing.
  
  
  RESULTS
  Morphologically, all HPs had a papillary and tubular architecture with a biphasic pattern of epithelial and myoepithelial cells. Immunohistochemistry revealed that oestrogen receptor expression was restricted to epithelial cells, whereas p63 and SMA were exclusively expressed in myoepithelial cells. The patterns of p53 and β-catenin immunostaining suggested wild-type genotypes. Direct sequencing revealed the presence of somaticPIK3CAmutations (Ex9. c.1633G>A, p.E545K and Ex20. c.3140A>G, p.H1047R) in two of the HPs and anAKT1(c.49G>A, p.E17K) mutation in one.BRAFandKRASmutations were not found in any of the HP cases.
  
  
  CONCLUSIONS
  PIK3CAandAKT1are frequently mutated in HP tumours (29% and 14%, respectively). PIK3CA/AKT1 pathway alterations in HP further support the hypothesis that HP is the vulvar (anogenital mammary-like gland) analogue of breast intraductal papilloma.
authors.affiliation: Department of Diagnostic Pathology, Kainan Hospital, Aichi, Japan.|Department of Pathology and Cytology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Goto
authors.affiliation: Department of Cellular and Organ Pathology, Graduate School of Medicine, Akita University, Akita, Japan.
authors.forename: Daichi
authors.initials: D
authors.lastname: Maeda
authors.affiliation: Department of Cellular and Organ Pathology, Graduate School of Medicine, Akita University, Akita, Japan.
authors.forename: Yukitsugu
authors.initials: Y
authors.lastname: Kudo-Asabe
authors.affiliation: Department of Pathology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hibiya
authors.affiliation: Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Akimasa
authors.initials: A
authors.lastname: Hayashi
authors.affiliation: Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
authors.affiliation: Department of Pathology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ohashi
authors.affiliation: Department of Cellular and Organ Pathology, Graduate School of Medicine, Akita University, Akita, Japan.
authors.forename: Akiteru
authors.initials: A
authors.lastname: Goto
mesh_terms: D018250:Acrospiroma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D058534:Class I Phosphatidylinositol 3-Kinases; D005260:Female; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D012878:Skin Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D013544:Sweat Gland Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D014846:Vulvar Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: GENETICS; GYNAECOLOGICAL PATHOLOGY; IMMUNOHISTOCHEMISTRY; SKIN TUMOURS