br CDH is a useful marker for
CDH17 NSC 232003 a useful marker for the histological diagnosis of human
GC. The targeting of CDH17 in GC can inhibit tumour growth and in-activate the NF-κB signalling pathway, concomitant with the inactiva-tion of oncogenes. Further investigation of CDH17-mediated oncogenic signalling and cognate molecular mechanisms will shed light on new targeted therapies for GC and, potentially, other gastrointestinal ma-lignancies.
The Education-Science Foundation for Middle-aged and Young Teachers of the Education Bureau of Fujian Province (JA13289). The Youth Foundation of Fujian Provincial Health and Family Planning Commission (2012-2-145). The Natural Science Foundation of Fujian Province, China (2017J0105).
Appendix A. Supplementary data
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CDX2 and Muc2 immunohistochemistry as prognostic markers in stage II colon cancer☆,☆☆,★
Matthew J. Cecchini MD, PhD a, , Joanna C. Walsh MB, BCh, MRCP(UK) FRCPC a, Jeremy Parfitt MD FRCPC a, Subrata Chakrabarti MBBS, PhD, FRCPC a, Rohann J. Correa MD, PhD b, Mary J. MacKenzie MD FRCPC c, David K. Driman MBChB, FRCPC a
aDepartment of Pathology and Laboratory Medicine London Health Sciences Centre, London, Ontario, Canada N6A 5A5 bDepartment of Oncology (Division of Radiation Oncology), London Regional Cancer Program, London, Ontario, Canada N6A 5W9 cDepartment of Oncology (Division of Medical Oncology), London Regional Cancer Program, London, Ontario, Canada N6A 5W9
Summary 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 sim-
ilar 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 pa-
thology 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 fo-
cally lost in 23% of cases. There was no difference in survival based on CDX2 expression, but Muc2 loss
icant 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 ex-
pression 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 prac-
tice. 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.
☆ Competing interest: The authors declare that they have no conflict of interest.
☆☆ Funding/Support: Grant support for this project was received from a resident research grant from Physicians' Services Incorporated Foundation and internal funding support from the Department of Pathology and Laboratory Medicine at Western University.