title: Calpain system protein expression in basal-like and triple-negative invasive breast cancer.
abstract: BACKGROUND
  Basal-like and triple-negative breast tumours encompass an important clinical subgroup and biomarkers that can prognostically stratify these patients are required.
  
  
  METHODS
  We investigated two breast cancer tissue microarrays for the expression of calpain-1, calpain-2 and calpastatin using immunohistochemistry. The first microarray was comprised of invasive tumours from 1371 unselected patients, and the verification microarray was comprised of invasive tumours from 387 oestrogen receptor (ER)-negative patients.
  
  
  RESULTS
  The calpain system contains a number of proteases and an endogenous inhibitor, calpastatin. Calpain activity is implicated in important cellular processes including cytoskeletal remodelling, apoptosis and survival. Our results show that the expression of calpastatin and calpain-1 are significantly associated with various clinicopathological criteria including tumour grade and ER expression. High expression of calpain-2 in basal-like or triple-negative disease was associated with adverse breast cancer-specific survival (P = 0.003 and <0.001, respectively) and was verified in an independent cohort of patients. Interestingly, those patients with basal-like or triple-negative disease with a low level of calpain-2 expression had similar breast cancer-specific survival to non-basal- or receptor- (oestrogen, progesterone or human epidermal growth factor receptor 2 (HER2)) positive disease.
  
  
  CONCLUSIONS
  Expression of the large catalytic subunit of m-calpain (calpain-2) is significantly associated with clinical outcome of patients with triple-negative and basal-like disease.
authors: Academic Oncology.
authors: S J
authors: SJ
authors: Storr
authors: Academic Oncology.
authors: K W
authors: KW
authors: Lee
authors: Academic Oncology.
authors: C M
authors: CM
authors: Woolston
authors: Academic Oncology.
authors: S
authors: S
authors: Safuan
authors: Histopathology, School of Molecular Medical Sciences, University of Nottingham.
authors: A R
authors: AR
authors: Green
authors: The Breast Institute, Nottingham University Hospitals NHS Trust, Nottingham.
authors: R D
authors: RD
authors: Macmillan
authors: Histopathology, School of Molecular Medical Sciences, University of Nottingham.
authors: A
authors: A
authors: Benhasouna
authors: Division of Nutritional Sciences, School of Biosciences, University of Nottingham, Loughborough, Leicestershire, UK.
authors: T
authors: T
authors: Parr
authors: Histopathology, School of Molecular Medical Sciences, University of Nottingham.
authors: I O
authors: IO
authors: Ellis
authors: Academic Oncology. Electronic address: stewart.martin@nottingham.ac.uk.
authors: S G
authors: SG
authors: Martin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D018295:Neoplasms, Basal Cell / Q000378:metabolism*; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D002135:Calcium-Binding Proteins; D002154:Calpain; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C033668:calpastatin; C508053:ERBB2 protein, human; C484806:CAPN1 protein, human; C569870:CAPN2 protein, human