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Storr, Sarah J. and Lee, K.W. and Woolston, Caroline M. and Safuan, Sabreena and Green, A.R. and Macmillan, R.D. and Benhasouna, A. and Parr, T. and Ellis, I.O. and Martin, Stewart G. (2012) Calpain system protein expression in basal-like and triple-negative invasive breast cancer. Annals of Oncology, 23 (9). pp. 2289-2296. ISSN 0923-7534

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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.

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