title: Tuberin and p27 expression in breast cancer patients with or without BRCA germline mutations.
abstract: BACKGROUND
  Tuberin, the protein product of tuberous sclerosis gene 2 (TSC2), is the functional component of the TSC1/TSC2 complex and regulates cell cycle through activation of the cyclin-dependent kinase inhibitor p27. The transcriptional regulation of p27 is, however, also linked to a functional BRCA protein, since in BRCA1 mutant breast cancer cells, which lack the ability to repair DNA damages by homologous recombination, p27 is down-regulated. We have therefore investigated the expression of both tuberin and p27 in normal breast tissue, and in malignant epithelium from women with and without a BRCA mutation.
  
  
  METHODS
  immunohistochemistry was used to compare p27 and tuberin protein expression in 26 BRCA1 and 2 mutation carriers, in 53 matched breast cancer patients without a family history, and in 74 benign breast tissues in a case-control study.
  
  
  RESULTS
  Tuberin and p27 protein expression were significantly more common in benign when compared to malignant breast tissue (p = 0.01 and p = 0.03), but no difference was observed when sporadic and BRCA-mutated breast cancer specimen were compared. Tuberin and p27 were positively correlated with each other (p = 0.0017, r = 0.2527). Furthermore, p27 expression was positively correlated with ER and PR, and negatively correlated with tumor size. The expression of tuberin and p27 in breast cancer was not correlated with clinical outcome.
  
  
  CONCLUSIONS
  Our results suggest that tuberin and p27 are aberrantly expressed in malignant tissue, but their expression does not appear to be dependent on the BRCA mutation state of a breast cancer patient.
authors.affiliation: Clinical Division of Gynaecology and Gynaecological Oncology, Department of Obstretrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Anne Catharina
authors.initials: AC
authors.lastname: Dressler
authors.forename: Gernot
authors.initials: G
authors.lastname: Hudelist
authors.forename: Anneliese
authors.initials: A
authors.lastname: Fink-Retter
authors.forename: Daphne
authors.initials: D
authors.lastname: Gschwantler-Kaulich
authors.forename: Georg
authors.initials: G
authors.lastname: Pfeiler
authors.forename: Margit
authors.initials: M
authors.lastname: Rosner
authors.forename: Markus
authors.initials: M
authors.lastname: Hengstschläger
authors.forename: Christian F
authors.initials: CF
authors.lastname: Singer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D019398:Genes, BRCA1; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis / Q000096:biosynthesis*; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D018809:Proliferating Cell Nuclear Antigen; C000624653:TSC2 protein, human; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; C413374:p27 antigen