Boecker Werner, Stenman Göran, Loening Thomas, Andersson Mattias K, Berg Tobias, Lange Alina, Bankfalvi Agnes, Samoilova Vera, Tiemann Katharina, Buchwalow Igor
Institute for Hematopathology, Fangdieckstr. 75A, 22547, Hamburg, Germany,
Virchows Arch. 2015 Jan;466(1):21-36. doi: 10.1007/s00428-014-1671-x. Epub 2014 Oct 26.
A small group of tumors of breast and salivary glands contains squamous/epidermoid elements as a constitutive feature (e.g., squamous carcinoma, syringomatous tumors, and mucoepidermoid carcinoma). Other tumors (e.g., pleomorphic adenoma, adenomyoepithelial tumors, and adenoid cystic carcinoma) may show occasionally squamous differentiation. Furthermore, squamous metaplasia may be observed in non-neoplastic breast and salivary tissues. However, the histogenesis of these squamous differentiations is far from being understood. Based on our earlier in situ triple immunofluorescence and quantitative reverse transcription (RT)-PCR experiments for basal keratins K5/14 and p63 as well as for glandular keratins (K7/K8/18), squamous keratins (K10 and K13), and myoepithelial lineage markers (smooth muscle actin, SMA), we here traced the squamous/epidermoid differentiation lineage of 60 tumors of the breast and/or salivary glands, cultured tumor cells of 2 tumors, and of 7 squamous metaplasias of non-neoplastic breast and salivary tissues. Our results indicate that both the neoplastic lesions as well as the non-neoplastic squamous metaplasia contain p63/K5/14+ cells that differentiate toward K10/13+ squamous cells. Thus, cells with squamous/epidermoid differentiation undergo a transition from its original p63/K5/14+ precursor state to K10/13+ squamous lineage state, which can be pictured by triple-immunofluorescence experiments. Given the immunophenotypic similarity of p63/K5/14+ tumor cells to their physiological p63/K5/14+ counterparts in normal breast and salivary duct epithelium, we suggest that these cells provide an important histogenetic key to understanding the pathogenesis of squamous differentiation both in normal breast/salivary gland tissues and their corresponding tumors.
一小部分乳腺和唾液腺肿瘤含有鳞状/表皮样成分，这是其本质特征（例如，鳞状细胞癌、汗腺样肿瘤和黏液表皮样癌）。其他肿瘤（例如，多形性腺瘤、腺肌上皮瘤和腺样囊性癌）偶尔也可能出现鳞状分化。此外，在非肿瘤性乳腺和唾液腺组织中可观察到鳞状化生。然而，这些鳞状分化的组织发生过程仍远未被理解。基于我们早期针对基底角蛋白K5/14和p63、腺性角蛋白（K7/K8/18）、鳞状角蛋白（K10和K13）以及肌上皮谱系标志物（平滑肌肌动蛋白，SMA）进行的原位三重免疫荧光和定量逆转录（RT）-PCR实验，我们在此追踪了60例乳腺和/或唾液腺肿瘤、2例肿瘤的培养肿瘤细胞以及7例非肿瘤性乳腺和唾液腺组织的鳞状化生的鳞状/表皮样分化谱系。我们的结果表明，肿瘤性病变以及非肿瘤性鳞状化生均含有向K10/13 + 鳞状细胞分化的p63/K5/14 + 细胞。因此具有鳞状/表皮样分化的细胞从其原始的p63/K5/14 + 前体状态转变为K10/13 + 鳞状谱系状态，这可以通过三重免疫荧光实验显示出来。鉴于p63/K5/14 + 肿瘤细胞与正常乳腺和唾液腺导管上皮中生理状态的p63/K5/14 + 对应细胞在免疫表型上的相似性，我们认为这些细胞为理解正常乳腺/唾液腺组织及其相应肿瘤中鳞状分化的发病机制提供了重要的组织发生学关键线索。
