Department of Pathology and Laboratory Medicine London Health Sciences Centre, London, Ontario, Canada N6A 5A5.
Department of Pathology and Laboratory Medicine London Health Sciences Centre, London, Ontario, Canada N6A 5A5.
Hum Pathol. 2019 Aug;90:70-79. doi: 10.1016/j.humpath.2019.05.005. Epub 2019 May 21.
The treatment for colorectal cancer is largely surgical followed by adjuvant chemotherapy in high-risk cases. In patients with stage II cancer, there is no clear benefit for chemotherapy, and the current tools for assessment of risk are inadequate. A recent study identified that colorectal cancer with a gene signature similar to undifferentiated colonic stem cells was associated with a worse outcome. It was later shown that loss of CDX2 detected by immunohistochemistry (IHC) alone resulted in a worse prognosis and that this could be used to predict patients who would benefit from chemotherapy. Having observed that CDX2 expression can be patchy, we elected to validate these prior results for clinical practice using whole-slide IHC. The pathology of all cases was reviewed, and 3 blocks were selected for CDX2 IHC. We also expanded the panel beyond CDX2 to assess whether other markers in the gene signature including CDX1, Muc2, GPX2, and villin could better predict outcome. Among 210 cases, CDX2 expression was diffusely lost in 11% and focally lost in 23% of cases. There was no difference in survival based on CDX2 expression, but Muc2 loss was associated with reduced survival (hazard ratio, 3.32; 95% confidence interval, 1.20 to 9.20). No significant differences in outcome were identified based on CDX1, GPX2, or villin expression. In keeping with this, assessment of The Cancer Genome Atlas gene expression data demonstrated that decreased Muc2 expression was associated with reduced overall survival. Our results with whole-slide IHC are different from the previous studies and caution against the use of CDX2 in isolation as a prognostic marker in clinical practice. We have identified that loss of Muc2 is associated with reduced survival. This supports the use of the colonic differentiation gene expression signature to identify high-risk patients but cautions against the use of any one IHC-based marker in isolation.
结直肠癌的治疗主要是手术，高危病例则需要辅助化疗。对于 II 期癌症患者，化疗并没有明显的益处，而且目前评估风险的工具也不充分。最近的一项研究发现，具有类似于未分化结肠干细胞基因特征的结直肠癌与更差的预后相关。后来发现，免疫组织化学（IHC）单独检测到 CDX2 的丢失会导致更差的预后，并且可以用来预测哪些患者将受益于化疗。我们观察到 CDX2 的表达可能是斑驳的，因此选择使用全切片 IHC 来验证这些先前的结果是否适用于临床实践。对所有病例的病理学进行了回顾，并选择了 3 个块进行 CDX2 IHC。我们还扩展了面板，评估基因特征中的其他标志物，包括 CDX1、Muc2、GPX2 和 villin，是否可以更好地预测预后。在 210 例病例中，CDX2 的表达在 11%的病例中弥漫性丢失，在 23%的病例中局灶性丢失。CDX2 表达与生存无差异，但 Muc2 丢失与生存减少相关（风险比，3.32；95%置信区间，1.20 至 9.20）。根据 CDX1、GPX2 或 villin 的表达，未发现结果有显著差异。与这一结果一致，对癌症基因组图谱基因表达数据的评估表明，Muc2 表达降低与总生存期缩短相关。我们使用全切片 IHC 的结果与之前的研究不同，不建议在临床实践中单独使用 CDX2 作为预后标志物。我们已经发现 Muc2 的丢失与生存减少相关。这支持使用结肠分化基因表达特征来识别高危患者，但不建议单独使用任何一种基于 IHC 的标志物。
