Tumor budding at the invasive front of colorectal cancer may not be associated with the epithelial-mesenchymal transition

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• 作者：Noriyuki Yamada ; CT^a ; Tamotsu Sugai ; MD^a ; ^{tsugai@iwate-med.ac.jp} ; Makoto Eizuka ; MD^a ; Koudai Tsuchida ; MD^a ; Ryo Sugimoto ; MD^a ; Yoshiharu Mue ; MD^a ; Masamichi Suzuki ; MD^a ; Mitsumasa Osakabe ; MD^a ; Noriyuki Uesugi ; MD^a ; Kazuyuki Ishida ; MD^a ; Kouki Otsuka ; MD^b ; Takayuki Matsumoto ; MD^c
• 关键词：Colorectal cancer ; Epithelial-mesenchymal transition ; Tumor budding ; TWIST ; ZEB1
• 刊名：Human Pathology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：60
• 期：Complete
• 页码：151-159
• 全文大小：1667 K
• 卷排序：60

文摘

Tumor budding is thought to reflect the epithelial-mesenchymal transition (EMT). However, the molecular mechanism linking tumor buds and the EMT remains unclear. Here, we examined the induction of tumor budding and EMT and their association with EMT-related proteins (ZEB1, TWIST, SNAIL, and SLUG) in colorectal cancer (CRC). Immunohistochemical expression of pan-cytokeratin was examined for identification of tumor budding in 101 CRCs. Grading of tumor budding was classified into low- and high-grade groups. Tissue microarray was conducted to identify tumor budding sites. The expression of E-cadherin, ZEB1, TWIST, SNAIL, and SLUG was examined in areas of tumor budding and the surrounding tumor stroma using a double-immunostaining method. Specifically, pan-cytokeratin and EMT-related proteins were assessed by double immunostaining. Low or no expression of E-cadherin was found in areas of tumor budding. Moreover, ZEB1, TWIST, SNAIL, and SLUG were not expressed in regions of tumor budding. However, the expression level of ZEB1 in the stromal cells surrounding tumor budding was significantly more frequent than that of TWIST, SNAI, and SLUG. In addition, the expression of EMT-related proteins in surrounding stromal cells was significantly greater in areas of high-grade tumor budding than in low-grade areas. Our present results suggest that EMT-related proteins play a minor role in forming tumor buds. In addition, our findings suggest the existence of subtypes of stromal cells in CRC with phenotypical and functional heterogeneity.