Prognostic Biomarker Found for Colon Cancer Patients

The majority of colon cancer patients whose tumors have started to travel to nearby tissue but no further are cured by surgery alone, but in a minority of these stage II colon cancer cases the cancer returns and the patients die.

The identification of high-risk stage II colon cancers is key to the selection of patients who require adjuvant treatment after surgery and microarray-based multigene-expression signatures derived from stem cells and progenitor cells hold promise, but they are difficult to use in clinical practice.

Scientists at the Columbia University Medical Center (New York, NY, USA) and their colleagues obtained colon-cancer tissue microarrays, fully annotated with clinical and pathological information, from three independent sources: 367 patients in the Cancer Diagnosis Program of the National Cancer Institute, 1,519 patients in the National Surgical Adjuvant Breast and Bowel Project C-07 trial, and 321 patients in the Stanford Tissue Microarray Database.

Formalin-fixed, paraffin-embedded tissue sections were stained with a mouse antihuman caudal-type homeobox transcription factor 2 (CDX2) monoclonal antibody that was previously validated for diagnostic applications (clone CDX2-88, BioGenex; Fremont, CA, USA). Tissue slides were stained on a Bond-Max automatic stainer and antigen detection was visualized with the use of the Bond Polymer Refine Detection kit (Leica Microsystems; Buffalo Grove, IL, USA). All tissue microarrays were scored for CDX2 expression in a blinded fashion and in cases in which tissue microarrays contained two tissue cores for a patient the two cores were scored independently and paired at the end.

Using a new bioinformatics approach, the team searched data from over 2,000 colon cancer patients and found 16 genes whose lack of expression is always tied to high levels of cancer stem cell markers. Of the 16 potential biomarkers, they found only one, the gene CDX2, for which a standardized test that detects its expression is already available. CDX2 regulates cell differentiation that is deciding the type of cell an immature stem cell matures into in the lining of the colon, which is where colon cancer starts. The team found that colon cancer patients whose tumors did not express CDX2 were more likely to relapse and die compared with patients whose tumors did express CDX2.

Piero Dalerba, MD, an assistant professor of medicine, pathology and cell biology, and lead author said, “We wanted to understand if the small group lacking CDX2 expression—approximately 4% of the global colon cancer population—fared poorly because of an intrinsic resistance to chemotherapy. To our surprise, we found that, on the contrary, tumors lacking CDX2 expression, despite being very aggressive from a biological point of view, also appeared to benefit from early treatment with adjuvant chemotherapy.” The study was published on January 21, 2016, in the New England Journal of Medicine (NEJM).

Related Links:
Columbia University Medical Center
BioGenex
Leica Microsystems