Details

Autor(en) / Beteiligte

• Satoh, Keisuke
• Nimura, Satoshi
• Aoki, Mikiko
• Hamasaki, Makoto
• Koga, Kaori
• Iwasaki, Hiroshi
• Yamashita, Yuichi
• Kataoka, Hiroaki
• Nabeshima, Kazuki

Titel

Tumor budding in colorectal carcinoma assessed by cytokeratin immunostaining and budding areas: Possible involvement of c‐Met

Ist Teil von

• Cancer science, 2014-11, Vol.105 (11), p.1487-1495

Ort / Verlag

England: John Wiley & Sons, Inc

Erscheinungsjahr

2014

Quelle

Wiley Online Library All Journals

Beschreibungen/Notizen

• Tumor budding/sprouting has been shown to be an independent adverse prognostic factor in T1 and T3N0 colorectal carcinomas, however, its assessment could be improved by more accurate identification of budding carcinoma cells and consideration of budding areas. Moreover, tumor budding mechanisms are yet to be defined. In this study, we evaluated the identification of budding tumor cells by either H&E staining alone or H&E with immunohistochemistry and developed a scoring system based on budding grades and areas. We examined whether the budding score correlated with clinicopathologic features and prognosis and the association between tumor budding/sprouting and c‐Met protein expression and phosphorylation and MET gene copy numbers because c‐Met is known to play an important role in colorectal carcinoma tumorigenesis. Cytokeratin immunohistochemistry could identify tumors with shorter disease‐free survival (DFS) from the low‐grade budding group assessed with H&E alone. High budding scores based on budding grade and area were more significantly correlated with DFS than scores obtained using the budding grade alone. In tumors with a high budding score, c‐Met expression and phosphorylation levels and MET gene copy numbers were significantly increased at the invasive front compared with those in superficial tumor portions. This study showed for the first time that high levels of phospho‐c‐Met at the invasive front were significantly associated with a high budding score and shorter DFS. In conclusion, a budding score assessed by budding grades and budding‐positive areas correlates highly with clinicopathologic aggressive features of colorectal carcinoma. Our study had two major aims: (1) To evaluate the associations between our scoring system for tumor budding/sprouting, which included budding grade and the proportion of budding‐positive areas, and clinicopathologic factors or prognosis; and (2) To assess the association between c‐Met expression and tumor budding/sprouting.