Shifting a Paradigm: a Molecular Approach to Staging Colorectal Cancer

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A quantitative, molecular analysis of lymph nodes in patients deemed colorectal cancer-free was found to be an effective predictor of recurrence, according to a study from researchers at the Kimmel Cancer Center at Jefferson and published online Feb 9. in Clinical Cancer Research.

Recurrence occurs in about 25 percent of node-negative patients (pN0), suggesting that occult metastases escaped detection, be it imaging modalities or histopathology.

To better predict recurrence and accurately stage these patients, Terry Hyslop, Ph.D. and Scott A. Waldman, M.D., Ph.D. of the Department of Pharmacology and Experimental Therapeutics of Thomas Jefferson University and the Kimmel Cancer Center at Jefferson, and colleagues explored a novel molecular approach, using the biomarker GUCY2C for metastatic colorectal cancer cells. 

Using 291 colorectal cancer patients who were node-negative, the researchers analyzed lymph nodes by histopathology and GUCY2C quantitative qRT-PCR. They were followed for a median of 24 months and categorized as having either low, intermediate or high tumor burdens.

The researchers had previously concluded that expression of GUCY2C increased risk of recurrence. However, it is apparent that nodal metastases do not assure recurrence; rather they indicate risk.

The researchers found that patients with greater occult tumor burden have a greater risk of recurrence compared to patients with less burden. Thus, molecular tumor burden in lymph nodes are independently associated with time to recurrence and disease-free survival in patients with node-negative colorectal cancer.

“This approach can improve prognostic risk stratification and chemotherapeutic allocation in pN0 patients,” the authors write. “More generally, this study reveals a previously unappreciated paradigm to advance cancer staging, clinically translating emerging molecular platforms that complement histopathology, laboratory diagnostic, and imaging modalities.”

For a copy of this study, please contact Steve Graff at

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Source: Thomas Jefferson University

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