Calpain system protein expression in basal-like and triple-negative invasive breast cancer
نویسندگان
چکیده
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.
منابع مشابه
High-throughput protein expression analysis using tissue microarray technology of a large well-characterised series identifies biologically distinct classes of breast cancer confirming recent cDNA
triple-negative breast cancers with distinct biological features. Jpn J Clin Oncol 2011; 41: 172–179. 10. Alexander BM, Sprott K, Farrow DA et al. DNA repair protein biomarkers associated with time to recurrence in triple-negative breast cancer. Clin Cancer Res 2010; 16: 5796–5804. 11. Mehta R, Jain RK, Sneige N et al. Expression of high-molecular-weight cytokeratin (34betaE12) is an independen...
متن کاملThe Prognostic Value of the Proliferation Marker Phosphohistone H3 (PPH3) in Luminal, Basal-Like and Triple Negative Phenotype Invasive Lymph Node-Negative Breast Cancer
PURPOSE Prognostic comparison of phosphohistone-H3 (PPH3) with Cytokeratin 5/6 and/or 14 positive (=basal-CK), triple (ER, PR, HER2)-negative (=TNP) and basal-like (=TNP and basal-CK positive) phenotype in invasive breast cancers. PATIENTS AND METHODS Classical variables, PPH3, ER, PR, basal-CK and HER2 in 240 T1-2N0M0 patients under 71 years. RESULTS TNP and basal-like cancers had higher P...
متن کاملGene Expression Changes in Pomegranate Peel Extract-Treated Triple-Negative Breast Cancer Cells
Background: Triple-negative breast cancer (TNBC) is treated with highly aggressive non-targeted chemotherapies. Safer and more effective therapeutic approaches than those currently in use are needed. Natural pomegranate peel extract (PPE) has recently been found to inhibit breast cancer progression; however, its mechanisms of action remain unclear. We hypothesized that transcriptional chan...
متن کاملApocrine carcinoma as triple-negative breast cancer: novel definition of apocrine-type carcinoma as estrogen/progesterone receptor-negative and androgen receptor-positive invasive ductal carcinoma.
OBJECTIVE Apocrine carcinoma, a subtype of invasive ductal carcinoma of the breast, expresses androgen receptor (AR), but often lacks estrogen receptor (ER) and progesterone receptor (PgR). In the present study, the author immunohistochemically defined apocrine-type carcinoma as ER-/PgR-/AR+ invasive ductal carcinoma and analyzed the significance of apocrine-type carcinoma as triple-negative br...
متن کاملUnderstanding and treating triple-negative breast cancer.
Triple-negative breast cancer is a subtype of breast cancer that is clinically negative for expression of estrogen and progesterone receptors (ER/PR) and HER2 protein. It is characterized by its unique molecular profile, aggressive behavior, distinct patterns of metastasis, and lack of targeted therapies. Although not synonymous, the majority of triple-negative breast cancers carry the "basal-l...
متن کامل