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This book chapter has been peer reviewed. It is the authors' final version prior to publication in Advances in Clinical Chemistry Volume 52, Issue C, 2010, Pages 19-39. The published version is available at DOI: 10.1016/S0065-2423(10)52007-9. Copyright © Elsevier Inc.


Tumor cells in regional lymph nodes are a key prognostic marker of survival and predictive marker of response to adjuvant chemotherapy in colorectal cancer. However, clinicopathologic techniques to detect lymph node metastases remain imperfect, and ~30% of patients with lymph nodes negative by histology (pN0) develop recurrent disease, reflecting occult metastases that escape detection. These observations underscore an unmet clinical need for accurate approaches to identify occult nodal metastases in colorectal cancer patients. GUCY2C is a receptor whose expression normally is restricted to intestinal epithelial cells, but is universally over-expressed by colorectal cancer cells. A prospective, multicenter, blinded clinical trial established the prognostic utility of GUCY2C qRT-PCR to detect occult nodal metastases in pN0 colorectal cancer patients. Molecular staging revealed that ~13% of pN0 patients were free of cancer cells, while ~87% had GUCY2C results that suggested occult metastases. The presence of occult nodal metastases was the most powerful independent predictor of time to recurrence and disease-free survival. These observations establish the utility of molecular detection of occult nodal metastases for assessing prognostic risk in pN0 colorectal cancer patients. Advancing GUCY2C into staging paradigms in clinical laboratories will require validation in independent patient populations, definition of the relationship between the quantity of occult tumor metastases and risk, and determination of the utility of GUCY2C qRT-PCR to identify pN0 patients who might benefit from adjuvant chemotherapy.



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