结直肠癌中的APC突变与肿瘤出芽
APC mutation and tumour budding in colorectal cancer.
作者信息
Jass J R, Barker M, Fraser L, Walsh M D, Whitehall V L J, Gabrielli B, Young J, Leggett B A
机构信息
Department of Molecular and Cellular Pathology, University of Queensland, Queensland 4006, Australia.
出版信息
J Clin Pathol. 2003 Jan;56(1):69-73. doi: 10.1136/jcp.56.1.69.
AIM
To determine the frequency of tumour budding and somatic APC mutation in a series of colorectal cancers stratified according to DNA microsatellite instability (MSI) status.
MATERIAL/METHODS: Ninety five colorectal cancers were genotyped for APC mutation in the mutation cluster region (exon 15) and scored for the presence of tumour budding at the invasive margin in haematoxylin and eosin stained sections. A subset was immunostained for beta catenin and p16.
RESULTS
The frequency of both somatic APC mutation and tumour budding increased pari passu in cancers stratified as sporadic MSI high (MSI-H), hereditary non-polyposis colorectal cancer (HNPCC), MSI low (MSI-L), and microsatellite stable (MSS). Both budding and APC mutation were significantly less frequent in sporadic MSI-H cancers than in MSI-L or MSS cancers. Tumour buds were characterised by increased immunostaining for both beta catenin and p16.
CONCLUSION
Tumour budding is associated with an adverse prognosis. The lack of budding in MSI-H colorectal cancer may account for the improved prognosis of this subset and may be explained by an intact WNT signalling pathway and/or inactivated p16(INK4a).
目的
在根据DNA微卫星不稳定性（MSI）状态分层的一系列结直肠癌中，确定肿瘤芽生和体细胞APC突变的频率。
材料/方法：对95例结直肠癌进行基因分型，检测其突变簇区域（外显子15）的APC突变情况，并对苏木精和伊红染色切片中浸润边缘的肿瘤芽生情况进行评分。对一个亚组进行β连环蛋白和p16免疫染色。
结果
在分为散发性微卫星高度不稳定（MSI-H）、遗传性非息肉病性结直肠癌（HNPCC）、微卫星低度不稳定（MSI-L）和微卫星稳定（MSS）的癌症中，体细胞APC突变和肿瘤芽生的频率同步增加。散发性MSI-H癌症中的芽生和APC突变频率均显著低于MSI-L或MSS癌症。肿瘤芽的特征是β连环蛋白和p16的免疫染色增加。
结论
肿瘤芽生与不良预后相关。MSI-H结直肠癌中缺乏芽生可能解释了该亚组预后的改善，并且可能由完整的WNT信号通路和/或失活的p16（INK4a）来解释。
Zotero 插件