The calpain system is associated with survival of breast cancer patients with large but operable inflammatory and non-inflammatory tumours treated with neoadjuvant chemotherapy - PubMed (original) (raw)

The calpain system is associated with survival of breast cancer patients with large but operable inflammatory and non-inflammatory tumours treated with neoadjuvant chemotherapy

Sarah J Storr et al. Oncotarget. 2016.

Abstract

The calpains are a family of intracellular cysteine proteases that function in a variety of important cellular functions, including cell signalling, motility, apoptosis and survival. In early invasive breast cancer expression of calpain-1, calpain-2 and their inhibitor, calpastatin, have been associated with clinical outcome and clinicopathological factors.The expression of calpain-1, calpain-2 and calpastatin was determined using immunohistochemistry on core biopsy samples, in a cohort of large but operable inflammatory and non-inflammatory primary breast cancer patients treated with neoadjuvant chemotherapy. Information on treatment and prognostic variables together with long-term clinical follow-up was available for these patients. Diagnostic pre-chemotherapy core biopsy samples and surgically excised specimens were available for analysis.Expression of calpastatin, calpain-1 or calpain-2 in the core biopsies was not associated with breast cancer specific survival in the total patient cohort; however, in patients with non-inflammatory breast cancer, high calpastatin expression was significantly associated with adverse breast cancer-specific survival (P=0.035), as was low calpain-2 expression (P=0.031). Low calpastatin expression was significantly associated with adverse breast cancer-specific survival of the inflammatory breast cancer patients (P=0.020), as was low calpain-1 expression (P=0.003).In conclusion, high calpain-2 and low calpastatin expression is associated with improved breast cancer-specific survival in non-inflammatory large but operable primary breast cancer treated with neoadjuvant chemotherapy. In inflammatory cases, high calpain-1 and high calpastatin expression is associated with improved breast cancer-specific survival. Determining the expression of these proteins may be of clinical relevance. Further validation, in multi-centre cohorts of breast cancer patients treated with neoadjuvant chemotherapy, is warranted.

Keywords: breast cancer; calpain; calpastatin; neoadjuvant chemotherapy; survival.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Figure 1

Figure 1. Representative photomicrographs following immunohistochemical staining of

A. low calpastatin, B. high calpastatin, C. low calpain-1, D. high calpain-1, E. low calpain-2 and F. high calpain-2 staining. Photomicrographs are shown at 100× magnification with 200× magnification inset box where scale bar shows 100μm.

Figure 2

Figure 2. Kaplan-Meier analysis of breast cancer specific survival showing the impact of high (black line) and low (grey line) calpastatin

A. and calpain-1 B. in patients with inflammatory breast cancer and calpastatin C. and calpain-2 D. expression in patients with non-inflammatory breast cancer in the core biopsy samples. Significance was determined using the log-rank test and the numbers shown below the Kaplan-Meier survival curves are the number of patients at risk at 0, 40, 80 and 120 months.

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