Zidar Nina, Boštjančič Emanuela, Malgaj Marija, Gale Nina, Dovšak Tadej, Didanovič Vojko
University of Ljubljana, Institute of Pathology, Faculty of Medicine, Korytkova 2, 1000, Ljubljana, Slovenia.
Department of Nephrology, University Clinical Center, Zaloška 7, Ljubljana, Slovenia.
Virchows Arch. 2018 Feb;472(2):237-245. doi: 10.1007/s00428-017-2192-1. Epub 2017 Jul 12.
Epithelial-mesenchymal transition (EMT) has emerged as a possible mechanism of cancer metastasizing, but strong evidence for EMT involvement in human cancer is lacking. Our aim was to compare oral spindle cell carcinoma (SpCC) as an example of EMT with oral conventional squamous cell carcinoma (SCC) with and without nodal metastases to test the hypothesis that EMT contributes to metastasizing in oral SCC. Thirty cases of oral SCC with and without nodal metastasis and 15 cases of SpCC were included. Epithelial (cytokeratin, E-cadherin), mesenchymal (vimentin, N-cadherin), and stem cell markers (ALDH-1, CD44, Nanog, Sox-2) and transcription repressors (Snail, Slug, Twist) were analyzed immunohistochemically. We also analyzed the expression of microRNAs miR-141, miR-200 family, miR-205, and miR-429. SpCC exhibited loss of epithelial markers and expression of mesenchymal markers or coexpression of both up-regulation of transcription repressors and down-regulation of the investigated microRNAs. SCC showed only occasional focal expression of mesenchymal markers at the invasive front. No other differences were observed between SCC with and without nodal metastases except for a higher expression of ALDH-1 in SCC with metastases. Our results suggest that SpCC is an example of true EMT but do not support the hypothesis that EMT is involved in metastasizing of conventional SCC. Regarding oral SCC progression and metastasizing, we have been facing a shift from the initial enthusiasm for the EMT concept towards a more critical approach with "EMT-like" and "partial EMT" concepts. The real question, though, is, is there no EMT at all?
上皮-间质转化（EMT）已成为癌症转移的一种可能机制，但缺乏EMT参与人类癌症的确凿证据。我们的目的是以口腔梭形细胞癌（SpCC）作为EMT的一个例子，与有或无淋巴结转移的口腔传统鳞状细胞癌（SCC）进行比较，以检验EMT有助于口腔SCC转移这一假设。纳入了30例有或无淋巴结转移的口腔SCC病例以及15例SpCC病例。采用免疫组织化学方法分析上皮标志物（细胞角蛋白、E-钙黏蛋白）、间质标志物（波形蛋白、N-钙黏蛋白）、干细胞标志物（醛脱氢酶-1、CD44、Nanog、Sox-2）以及转录抑制因子（Snail、Slug、Twist）。我们还分析了微小RNA miR-141、miR-200家族、miR-205和miR-429的表达情况。SpCC表现出上皮标志物缺失和间质标志物表达，或转录抑制因子上调与所研究微小RNA下调的共表达。SCC仅在侵袭前沿偶尔出现间质标志物的局灶性表达。有或无淋巴结转移的SCC之间未观察到其他差异，只是有转移的SCC中醛脱氢酶-1的表达较高。我们的结果表明，SpCC是真正EMT的一个例子，但不支持EMT参与传统SCC转移的假设。关于口腔SCC的进展和转移，我们正面临着从最初对EMT概念的热情转向采用“EMT样”和“部分EMT”概念的更为批判性的方法。然而，真正的问题是，根本不存在EMT吗？
