Clinical Department of Pathology and Cytology, Clinical Hospital Center Rijeka, Krešimirova 42, 51000 Rijeka, Croatia.
Clinical Department of Pathology and Cytology, Clinical Hospital Center Rijeka, Krešimirova 42, 51000 Rijeka, Croatia; Department of Pathology, Faculty of Medicine, University of Rijeka, Brace Branchetta 20, 51000 Rijeka, Croatia.
Pathol Res Pract. 2020 Sep;216(9):153068. doi: 10.1016/j.prp.2020.153068. Epub 2020 Jun 20.
Breast cancer is a heterogeneous disease with different biological outcome and ability to acquire resistance to therapy. The calpain family of proteases and androgen receptor (AR) are implicated in breast cancer pathogenesis and progression and are potential targets for novel treatment regimens. The aim of this study was to investigate the expression of calpain-1 and AR in breast cancer and to correlate their expression with clinicopathological variables and prognosis of patients. In this study we enrolled 219 breast cancer patients with long term follow-up information available. Immunohistochemical methods on a tissue microarray were used to investigate expression of calpain-1 and AR in tumor cells. The expression of calpain-1 and AR both differed significantly between the tumor subtypes of patients (p = 0.002 and p = 0.042 respectively). High calpain-1 expression was associated with patient's age over 50 years (p = 0.005) and positive ER status (p = 0.009), but not with other clinicopathological variables. Women with AR negative breast cancers were more likely to be older (p = 0.016), to have bigger tumors (p = 0.032), higher stage of the disease (p = 0.026), presence of exulceration (p = 0.017), negative ER status (p = 0.007) and higher Ki-67 proliferative index (p = 0.027). Calpain-1 expression was not associated with breast cancer specific overall survival in the total cohort of patients, however low calpain-1 expression was associated with adverse survival (p = 0.018) in triple negative subgroup of patients. Low calpain-1 expression was also associated with significantly shorter 5-year disease-free survival in total cohort of patients (p = 0.03). AR status was not associated with overall and disease-free survival of patients. This study has demonstrated that the expression of calpain-1 and androgen receptors are associated with important clinicopathological variables. The expression of calpain-1 was associated with improved disease-free survival of all analyzed patients and with improved overall survival of triple negative breast cancer patients.
乳腺癌是一种具有不同生物学结局和获得治疗耐药能力的异质性疾病。钙蛋白酶家族蛋白酶和雄激素受体 (AR) 参与乳腺癌的发病机制和进展，是新型治疗方案的潜在靶点。本研究旨在探讨钙蛋白酶-1 和 AR 在乳腺癌中的表达，并将其表达与患者的临床病理变量和预后相关联。在本研究中，我们招募了 219 名具有长期随访信息的乳腺癌患者。使用组织微阵列的免疫组织化学方法来研究肿瘤细胞中钙蛋白酶-1 和 AR 的表达。钙蛋白酶-1 和 AR 的表达在患者的肿瘤亚型之间存在显著差异（p=0.002 和 p=0.042）。高钙蛋白酶-1 表达与患者年龄大于 50 岁（p=0.005）和阳性 ER 状态相关（p=0.009），但与其他临床病理变量无关。AR 阴性乳腺癌患者更有可能年龄较大（p=0.016），肿瘤较大（p=0.032），疾病分期较高（p=0.026），存在溃疡（p=0.017），ER 状态阴性（p=0.007）和 Ki-67 增殖指数较高（p=0.027）。钙蛋白酶-1 的表达与患者的总生存时间无关，但在三阴性乳腺癌亚组中，低钙蛋白酶-1 表达与不良生存相关（p=0.018）。低钙蛋白酶-1 表达也与患者总队列的 5 年无病生存率显著缩短相关（p=0.03）。AR 状态与患者的总生存时间和无病生存时间无关。本研究表明钙蛋白酶-1 和雄激素受体的表达与重要的临床病理变量相关。钙蛋白酶-1 的表达与所有分析患者的无病生存率提高以及三阴性乳腺癌患者的总生存率提高相关。
