Rasotto R, Goldschmidt M H, Castagnaro M, Carnier P, Caliari D, Zappulli V
Pathology Department, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU, UK.
Laboratory of Pathology and Toxicology, Department of Pathobiology, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, PA 19104, USA.
J Comp Pathol. 2014 Aug-Oct;151(2-3):166-80. doi: 10.1016/j.jcpa.2014.04.013. Epub 2014 Jun 27.
Basal-like tumours constitute 2-18% of all human breast cancers (HBCs). These tumours have a basal myoepithelial phenotype and it has been hypothesized that they originate from either myoepithelial cells or mammary progenitor cells. They are heterogeneous in morphology, clinical presentation, outcome and response to therapy. Canine mammary carcinomas (CMCs) have epidemiological and biological similarities to HBCs, are frequently biphasic and are composed of two distinct neoplastic populations (epithelial and myoepithelial). The present study evaluates the potential of CMCs as a natural model for basal-like HBCs. Single and double immunohistochemistry was performed on serial sections of 10 normal canine mammary glands and 65 CMCs to evaluate expression of cytokeratin (CK) 8/18, CK5, CK14, α-smooth muscle actin (SMA), calponin (CALP), p63 and vimentin (VIM). The tumours were also evaluated for Ki67 and human epidermal growth factor receptor (HER)-2 expression. A hierarchical model of cell differentiation was established, similar to that for the human breast. We hypothesized that progenitor cells (CK5(+), CK14(+), p63(+) and VIM(+)) differentiate into terminally-differentiated luminal glandular (CK8/18(+)) and myoepithelial (CALP(+), SMA(+) and VIM(+)) cells via intermediary luminal glandular cells (CK5(+), CK14(+) and CK8/CK18(+)) and intermediary myoepithelial cells (CK5(+), CK14(+), p63(+), SMA(+), CALP(+) and VIM(+)). Neoplastic myoepithelial cells in canine complex carcinomas had labelling similar to that of terminally-differentiated myoepithelial cells, while those of carcinomas-and-malignant myoepitheliomas with a more aggressive biological behaviour (i.e. higher frequency of vascular/lymph node invasion and visceral metastases and higher risk of tumour-related death) were comparable with intermediary myoepithelial cells and had significantly higher Ki67 expression. The majority of CMCs examined were negative for expression of HER-2. The biphasic appearance of CMCs with involvement of the myoepithelial component in different stages of cell differentiation may help to define the role of myoepithelial cells in the mammary carcinogenetic process and the heterogeneous nature of basal-like HBCs.
基底样肿瘤占所有人类乳腺癌（HBC）的2%-18%。这些肿瘤具有基底肌上皮表型，据推测它们起源于肌上皮细胞或乳腺祖细胞。它们在形态、临床表现、预后及对治疗的反应方面具有异质性。犬乳腺癌（CMC）在流行病学和生物学特性上与HBC相似，常呈双相性，由两种不同的肿瘤细胞群（上皮细胞和肌上皮细胞）组成。本研究评估了CMC作为基底样HBC天然模型的潜力。对10个正常犬乳腺和65个CMC的连续切片进行单重和双重免疫组化，以评估细胞角蛋白（CK）8/18、CK5、CK14、α-平滑肌肌动蛋白（SMA）、钙调蛋白（CALP）、p63和波形蛋白（VIM）的表达。还评估了肿瘤的Ki67和人表皮生长因子受体（HER）-2表达。建立了一个类似于人类乳腺的细胞分化层次模型。我们假设祖细胞（CK5(+)、CK14(+)、p63(+)和VIM(+)）通过中间腔腺细胞（CK5(+)、CK14(+)和CK8/CK18(+)）和中间肌上皮细胞（CK5(+)、CK14(+)、p63(+)、SMA(+)、CALP(+)和VIM(+)）分化为终末分化的腔腺（CK8/18(+)）和肌上皮（CALP(+)、SMA(+)和VIM(+)）细胞。犬复合癌中的肿瘤性肌上皮细胞标记与终末分化的肌上皮细胞相似，而具有更具侵袭性生物学行为（即血管/淋巴结侵犯和内脏转移频率更高以及肿瘤相关死亡风险更高）的癌和恶性肌上皮瘤中的肿瘤性肌上皮细胞与中间肌上皮细胞相当，且Ki67表达显著更高。大多数检测的CMC的HER-2表达为阴性。CMC的双相外观以及肌上皮成分在细胞分化不同阶段的参与情况，可能有助于确定肌上皮细胞在乳腺癌发生过程中的作用以及基底样HBC的异质性本质。
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