title: Intraductal carcinoma is the precursor of carcinoma ex pleomorphic adenoma and is often associated with dysfunctional p53.
abstract: OBJECTIVE
  Although intraductal carcinoma has been demonstrated in intracapsular carcinoma ex pleomorphic adenoma (CEPA), the morphological and genetic stages of transformation of pleomorphic adenoma (PA) to CEPA are not fully understood. The aim of this study was to investigate the morphology of intracapsular CEPA.
  
  
  RESULTS
  The largest series of intracapsular CEPA studied was subject to immunohistochemical double-staining to detect p53 protein and cellular proliferation in different types of cell combined with mutational analysis of the p53 gene in laser-microdissected material. Intraductal carcinoma with high-grade cellular atypia and frequent accumulation of p53 protein was found in 15/19 cases. Purely intraductal carcinoma was found in eight cases. Mutation of p53 was found in 7/19 cases, of which it was found in intraductal carcinoma in 5/15 cases.
  
  
  CONCLUSIONS
  The frequent demonstration of intraductal carcinoma indicates that this preinvasive lesion is likely to be a constant feature in the malignant transformation of PA to CEPA. It appears to be a feature of CEPA developing from both primary and recurrent PA. The combined immunohistochemical and genetic data show that 14/19 cases of CEPA and 11/15 cases with intraductal carcinoma showed genetic or morphological evidence of dysfunctional p53, indicating that this is an early event in malignant transformation.
authors.affiliation: Institute of Pathology, Ludwig Maximilian University, Munich, Germany. stephan.ihrler@med.uni-muenchen.de
authors.forename: S
authors.initials: S
authors.lastname: Ihrler
authors.forename: C
authors.initials: C
authors.lastname: Weiler
authors.forename: A
authors.initials: A
authors.lastname: Hirschmann
authors.forename: A
authors.initials: A
authors.lastname: Sendelhofert
authors.forename: S
authors.initials: S
authors.lastname: Lang
authors.forename: O
authors.initials: O
authors.lastname: Guntinas-Lichius
authors.forename: G
authors.initials: G
authors.lastname: Arnold
authors.forename: C
authors.initials: C
authors.lastname: Zietz
authors.forename: J D
authors.initials: JD
authors.lastname: Harrison
mesh_terms: D008949:Adenoma, Pleomorphic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053547:Keratin-14 / Q000032:analysis; D053552:Keratin-7 / Q000032:analysis; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009154:Mutation; D012468:Salivary Gland Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012470:Salivary Glands, Minor / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000235:genetics
chemical_list: D053547:Keratin-14; D053552:Keratin-7; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53