Caliari Diego, Zappulli Valentina, Rasotto Roberta, Cardazzo Barbara, Frassineti Federica, Goldschmidt Michael H, Castagnaro Massimo
BMC Vet Res. 2014 Sep 25;10:185. doi: 10.1186/s12917-014-0185-8.
Human breast cancer is a heterogeneous disease classified by molecular subtyping into luminal A, luminal B, HER2-overexpressing, basal-like, claudin-low and normal-breast like. The routinely applied and standardized immunohistochemical-based surrogates of this classification group together the last three entities as triple-negative breast cancer (TNBCs) that show the most diverse and complex heterogeneity and represent a therapeutic challenge. In the present work 156 feline mammary lesions consisting of feline mammary carcinomas (FMCs), benign neoplasms, and hyperplastic/dysplastic tissues were evaluated histologically and by immunohistochemistry for expression of basal and luminal cytokeratins (CK), vimentin, alpha-smooth muscle actin, calponin, estrogen receptor (ER) alpha (a), and progesterone receptor (PR). Thirty-seven FMCs with 27 matched non-neoplastic controls were also investigated for gene expression of ERa, ER beta, PR, and HER2.
A large group of hormone receptors (HRs)-negative aggressive carcinomas - that did not overexpress HER2 - could be distinguished from the less aggressive (10.8%) and benign (8%) HRs + tumors, that showed bilineage (luminal and myoepithelial) differentiation. Immunohistochemical evaluations of cytoplasmic filaments indicated that HRs- FMCs are vimentin+, CK14+, and CK5_6+ carcinomas that may resemble the TNBCs (basal like/claudin low) described in women. The identification of luminal and myoepithelial progenitors within the mammary ductal system suggested potential cells/sites of origin of these tumors. A diffuse and never previously described CKs/vimentin luminal cell co-expression was detected in the non-neoplastic ducts, indicating a potential bilineage progenitor.
These results indicate and potentially explain the high incidence of triple-negative, vimentin + aggressive tumors in cats that may used to elucidate some of the challenging features of TNBCs in women.
人类乳腺癌是一种异质性疾病，根据分子亚型可分为腔面A型、腔面B型、HER2过表达型、基底样型、Claudin低表达型和正常乳腺样型。这种分类中常规应用且标准化的基于免疫组织化学的替代指标将最后三种实体归为三阴性乳腺癌（TNBC），其显示出最多样化和复杂的异质性，是一个治疗挑战。在本研究中，对156例猫乳腺病变（包括猫乳腺癌（FMC）、良性肿瘤和增生/发育异常组织）进行了组织学和免疫组织化学评估，检测基底和腔面细胞角蛋白（CK）、波形蛋白、α平滑肌肌动蛋白、钙调蛋白、雌激素受体（ER）α（α）和孕激素受体（PR）的表达。还对37例FMC及其27例匹配的非肿瘤对照进行了ERα、ERβ、PR和HER2的基因表达研究。
一大组不表达HER2的激素受体（HR）阴性侵袭性癌可与侵袭性较弱（10.8%）和良性（8%）的HR阳性肿瘤区分开来，后者显示双谱系（腔面和肌上皮）分化。细胞质丝的免疫组织化学评估表明，HR阴性FMC是波形蛋白阳性、CK14阳性和CK5_6阳性癌，可能类似于女性中描述的TNBC（基底样/Claudin低表达型）。乳腺导管系统内腔面和肌上皮祖细胞的鉴定提示了这些肿瘤的潜在细胞/起源部位。在非肿瘤导管中检测到一种弥漫性且此前从未描述过的CKs/波形蛋白腔面细胞共表达，表明存在潜在的双谱系祖细胞。
这些结果表明并可能解释了猫中三阴性、波形蛋白阳性侵袭性肿瘤的高发病率，这可能有助于阐明女性TNBC的一些具有挑战性的特征。
