Tumor budding in colorectal carcinoma assessed by cytokeratin immunostaining and budding areas: possible involvement of c-Met.
Tumor budding in colorectal carcinoma assessed by cytokeratin immunostaining and budding areas: possible involvement of c-Met.
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DOI：
10.1111/cas.12530
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发表时间：
2014-11
期刊：
影响因子：
5.7
通讯作者：
Nabeshima K
中科院分区：
文献类型：
--
作者：
Satoh K;Nimura S;Aoki M;Hamasaki M;Koga K;Iwasaki H;Yamashita Y;Kataoka H;Nabeshima K
肿瘤出芽/出芽已被证明是 T1 和 T3N0 结直肠癌的独立不良预后因素，然而，可以通过更准确地识别出芽癌细胞和考虑出芽区域来改善其评估。此外，肿瘤出芽机制尚未明确。在这项研究中，我们通过单独的 H&E 染色或 H&E 结合免疫组织化学评估了对出芽肿瘤细胞的识别，并开发了一个基于出芽等级和面积的评分系统。我们检查了出芽评分是否与临床病理特征和预后相关，以及肿瘤出芽/发芽与 c-Met 蛋白表达、磷酸化和 MET 基因拷贝数之间的关联，因为已知 c-Met 在结直肠癌肿瘤发生中发挥重要作用。细胞角蛋白免疫组织化学可以从仅使用 H&E 评估的低级别出芽组中识别出无病生存期 (DFS) 较短的肿瘤。与单独使用出芽等级获得的分数相比，基于出芽等级和面积的高出芽分数与 DFS 的相关性更显着。在出芽评分高的肿瘤中，与浅表肿瘤部分相比，侵袭前沿的 c-Met 表达和磷酸化水平以及 MET 基因拷贝数显着增加。这项研究首次表明，侵入前沿的高水平磷酸-c-Met 与高出芽评分和较短的 DFS 显着相关。总之，通过出芽等级和出芽阳性区域评估的出芽评分与结直肠癌的临床病理侵袭性特征高度相关。
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.
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影响因子：
6.4
作者：
Shinto, E;Mochizuki, H;Jass, JR
通讯作者：
Jass, JR
影响因子：
11.2
作者：
Jedeszko C;Victor BC;Podgorski I;Sloane BF
通讯作者：
Sloane BF
影响因子：
3.4
作者：
Matsumoto, Shinji;Nabeshima, Kazuki;Tsujimura, Tohru
通讯作者：
Tsujimura, Tohru
影响因子：
2.8
作者：
Losi, Lorena;Ponti, Giovanni;de Leon, Maurizio Ponz
通讯作者：
de Leon, Maurizio Ponz
影响因子：
3.9
作者：
Shinto, Eiji;Jass, Jeremy R.;Matsubara, Osamu
通讯作者：
Matsubara, Osamu