Micello Donata, Bossi Alberto, Marando Alessandro, Dainese Emanuele, Sessa Fausto, Capella Carlo
Anatomic Pathology Unit, Multimedica, via Fantoli 16/15, 20138, Milan, Italy.
Institute of Molecular Science and Technologies of the CNR, CNR-ISTM, via Fantoli 16/15, 20138, Milan, Italy.
Virchows Arch. 2017 Jul;471(1):13-21. doi: 10.1007/s00428-017-2149-4. Epub 2017 May 26.
Calretinin expression has been reported in neoplasms arising in various organs, including the breast. We investigated the relationship of calretinin expression with different histological and molecular subtypes of invasive breast carcinomas (IBCs) and its prognostic significance in high-grade female hormone receptor-negative IBCs. A total of 196 cases of IBCs of different histological subtypes were analyzed for immunohistochemical expression of calretinin, human epidermal growth factor receptor 2 (HER2), basal-like (BL), apocrine, and proliferative markers and grouped in different molecular subtypes. We found significant morphological differences in the group of formally classified invasive ductal carcinoma of no special type (IDC-NST), which we further subdivided into two types (type I IDC-NST and type II IDC-NST) according to their morphology. Calretinin expression was found in 55.1% of the IBCs and was strongly associated with carcinoma with medullary features (P = 0.014) and type II IDC-NST (P < 0.001), while type I IDC-NST correlated (P < 0.001) with a lack of calretinin expression. Among the molecular subtypes of IBC, calretinin expression was identified in a significant portion of BL breast cancers (BLBCs), while expression was poor in HER2-overexpressing and molecular-apocrine (MA) HER2-negative subtypes and even less in MA/HER2+ ones. Calretinin expression was significantly associated with high (≥50) Ki-67 (P = 0.02), but not with parameters like age, tumor size, lymph node status, overall survival (OS), and disease-free survival. Calretinin expression is most common in high-grade IBCs with histological medullary features, type II IDC-NST and BL phenotype, and is associated with high neoplastic proliferative index.
据报道，钙视网膜蛋白在包括乳腺在内的各种器官发生的肿瘤中均有表达。我们研究了钙视网膜蛋白表达与浸润性乳腺癌（IBC）不同组织学和分子亚型的关系及其在高级别女性激素受体阴性IBC中的预后意义。对196例不同组织学亚型的IBC进行分析，检测钙视网膜蛋白、人表皮生长因子受体2（HER2）、基底样（BL）、大汗腺和增殖标志物的免疫组化表达，并将其分为不同的分子亚型。我们发现，在正式分类的非特殊类型浸润性导管癌（IDC-NST）组中存在显著的形态学差异，根据其形态我们进一步将其细分为两种类型（I型IDC-NST和II型IDC-NST）。在55.1%的IBC中发现了钙视网膜蛋白表达，其与具有髓样特征的癌（P = 0.014）和II型IDC-NST（P < 0.001）密切相关，而I型IDC-NST与钙视网膜蛋白表达缺失相关（P < 0.001）。在IBC的分子亚型中，在相当一部分BL乳腺癌（BLBC）中发现了钙视网膜蛋白表达，而在HER2过表达和分子大汗腺（MA）HER2阴性亚型中表达较差，在MA/HER2+亚型中表达更少。钙视网膜蛋白表达与高（≥50）Ki-67显著相关（P = 0.02），但与年龄、肿瘤大小、淋巴结状态、总生存期（OS）和无病生存期等参数无关。钙视网膜蛋白表达在具有组织学髓样特征、II型IDC-NST和BL表型的高级别IBC中最为常见，并且与高肿瘤增殖指数相关。
