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Ann Oncol. 2012 Sep;23(9):2289-96. doi: 10.1093/annonc/mds176. Epub 2012 Jun 27.

Calpain system protein expression in basal-like and triple-negative invasive breast cancer.

Author information

1
Academic Oncology, School of Molecular Medical Sciences, University of Nottingham, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham NG5 1PB, UK.

Abstract

BACKGROUND:

Basal-like and triple-negative breast tumours encompass an important clinical subgroup and biomarkers that can prognostically stratify these patients are required.

MATERIALS AND 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.

PMID:
22745213
PMCID:
PMC3425372
DOI:
10.1093/annonc/mds176
[Indexed for MEDLINE]
Free PMC Article
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