The calpain system is associated with survival of breast cancer patients with large but operable inflammatory and non-inflammatory tumours treated with neoadjuvant chemotherapy
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Sarah J. Storr1, Siwei Zhang1, Tim Perren2,3, Mark Lansdown2, Hiba Fatayer3, Nisha Sharma4, Renu Gahlaut2, Abeer Shaaban2,5, Stewart G. Martin1
1Department of Clinical Oncology, Division of Cancer and Stem Cells, University of Nottingham, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, NG5 1PB, UK
2Leeds Institute of Cancer Medicine and Pathology, St James’s Institute of Oncology, St James’s University Hospital, Leeds, LS9 7TF, UK
3Department of Breast Surgery, St James’s University Hospital, Leeds, LS9 7TF, UK
4Breast Screening Unit Leeds/Wakefield, Seacroft Hospital, Leeds, LS14 6UH, UK
5Department of Histopathology, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Queen Elizabeth Medical Centre and the University of Birmingham, Birmingham, B15 2TH, UK
Stewart G. Martin, email: [email protected]
Keywords: calpain, calpastatin, breast cancer, neoadjuvant chemotherapy, survival
Received: February 25, 2016 Accepted: May 29, 2016 Published: June 15, 2016
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.
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