Institute of Pathology, University of Bern, Bern, Switzerland.
Histopathology. 2012 Nov;61(5):777-87. doi: 10.1111/j.1365-2559.2012.04273.x. Epub 2012 Jul 16.
In colorectal cancer, tumour budding, a process likened to epithelial mesenchymal transition, is an adverse prognostic factor which is rarely found in tumours with high-level microsatellite instability (MSI-H). Cases with MSI-H or high-level CpG island methylator phenotype (CIMP-H) have similar histomorphological features, yet seemingly opposite prognosis. We hypothesized that tumour budding is related to CIMP, thus partially explaining this prognostic difference.
MSI, KRAS, BRAF, CIMP and 0(6)-methylguanine-DNA methyltransferase (MGMT) were investigated in tissues from 127 colorectal cancer patients. Tumour budding was scored using pan-cytokeratin-stained whole tissue sections within the densest area of buds (×40). Tumour budding was not associated with KRAS, BRAF, MGMT or CIMP, but was correlated inversely with MSI-H (P = 0.0049). Multivariate survival time analysis revealed that tumour budding was independent of all five molecular features and was predicted by MSI status [odds ratio (OR): 4.29, 95% confidence interval (CI) 1.5-12.1; P = 0.006)], but not CIMP (OR: 0.81, 95% CI 0.3-2.5; P = 0.714).
These findings underline that MSI, rather than CIMP, plays a role in conferring a tumour budding phenotype. Budding retains its unfavourable prognostic effect independently of these five molecular features. Continued efforts to standardize the assessment of tumour budding are necessary to integrate this feature into daily diagnostic routine.
在结直肠癌中，肿瘤芽殖是一种类似于上皮间质转化的过程，是一种不良的预后因素，在高水平微卫星不稳定（MSI-H）的肿瘤中很少发现。具有 MSI-H 或高水平 CpG 岛甲基化表型（CIMP-H）的病例具有相似的组织形态学特征，但预后似乎相反。我们假设肿瘤芽殖与 CIMP 有关，从而部分解释了这种预后差异。
在 127 例结直肠癌患者的组织中研究了 MSI、KRAS、BRAF、CIMP 和 O(6)-甲基鸟嘌呤-DNA 甲基转移酶（MGMT）。使用最密集芽殖区域内的 pan-细胞角蛋白染色全组织切片对肿瘤芽殖进行评分（×40）。肿瘤芽殖与 KRAS、BRAF、MGMT 或 CIMP 无关，但与 MSI-H 呈负相关（P = 0.0049）。多变量生存时间分析显示，肿瘤芽殖独立于所有五个分子特征，并且由 MSI 状态预测[优势比（OR）：4.29，95%置信区间（CI）1.5-12.1；P = 0.006]，而不是 CIMP（OR：0.81，95% CI 0.3-2.5；P = 0.714）。
这些发现强调了 MSI 而不是 CIMP 在赋予肿瘤芽殖表型方面发挥作用。芽殖独立于这五个分子特征保留其不利的预后作用。需要继续努力规范肿瘤芽殖的评估，将这一特征纳入日常诊断常规。
