title: Loss of heterozygosity is detected at chromosomes 1p35-36 (NB), 3p25 (VHL), 16p13 (TSC2/PKD1), and 17p13 (TP53) in microdissected apocrine carcinomas of the breast.
abstract: BACKGROUND
  Apocrine carcinomas of the breast are an unusual special category of predominantly AR+, ER-, and PR- breast cancer, characterized by cells with abundant, eosinophilic cytoplasm and nuclei with often prominent nucleoli. To further investigate these lesions, loss of heterozygosity (LOH) was evaluated at multiple chromosomal loci, including loci frequently mutated in breast cancer.
  
  
  METHODS
  Twenty-five intraductal apocrine carcinomas, 11 invasive apocrine carcinomas, and six apocrine hyperplasias were retrieved from the files of the Armed Forces Institute of Pathology (Washington, DC) and Fairfax Hospital (Fairfax, VA). Cells from lesional as well as normal tissues were microdissected. LOH was performed at a number of chromosomal loci, including loci commonly altered in breast cancer: 1p35-36 (NB), 3p25.5 (VHL), 8p12 (D8S136), 9p21 (p16), 11p13 (D11S904), 11q13 (INT-2 and PYGM), 16p13.3 (TSC2/PKD1 gene region), 17p13 (TP53), 17q13 (NM23), and 22q12 (D22S683).
  
  
  RESULTS
  Among informative in situ and invasive apocrine carcinomas, LOH was present in 33% of 15 cases for 17p13 (TP53), as well as 36% of 14 cases for 3p25 (VHL), 30% of 10 cases for 1p35-36 (NB), and 27% of 11 cases for 16p13.3 (TSC2/PKD1). A higher frequency of LOH was noted among invasive apocrine carcinomas (30 to 50%) compared with in situ apocrine carcinomas (23 to 33%) at these loci. LOH was present simultaneously for TP53 and either VHL or NB in five cases. Infrequent (< or =12%) or absent LOH was detected at the remaining loci, including several loci commonly mutated in breast cancer (i.e., INT2, PYGM, and NM23). LOH was not detected in any of the six apocrine hyperplasias.
  
  
  CONCLUSIONS
  An intermediate frequency of allelic loss was detected at multiple tumor suppressor gene loci, including 17p13 (TP53), as well as 1p35-336 (NB), 3p25 (VHL), and 16p13 (PKD1/ TSC2), in apocrine carcinomas of the breast, with a higher overall frequency of LOH noted among invasive tumors compared with in situ tumors. Aside from LOH at p53, LOH was infrequent or absent at several other loci commonly mutated in breast cancer. This preliminary molecular evidence supports immunohistochemical data that apocrine carcinomas of the breast may possess unique mechanisms of carcinogenesis, compared with ordinary ductal carcinomas. However, further study is needed to support this assertion and to determine if the LOH detected is truly etiologic or if it is the result of genetic progression.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill 27599-7525, USA. lininger@med.unc.edu
authors.forename: R A
authors.initials: RA
authors.lastname: Lininger
authors.forename: Z
authors.initials: Z
authors.lastname: Zhuang
authors.forename: Y
authors.initials: Y
authors.lastname: Man
authors.forename: W S
authors.initials: WS
authors.lastname: Park
authors.forename: M
authors.initials: M
authors.lastname: Emmert-Buck
authors.forename: F A
authors.initials: FA
authors.lastname: Tavassoli
mesh_terms: D000483:Alleles; D001050:Apocrine Glands / Q000473:pathology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics / Q000473:pathology; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D016133:Polymerase Chain Reaction; D013544:Sweat Gland Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm