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Mejia A , Schulz S , Hyslop T , Weinberg DS , Waldman SA
GUCY2C reverse transcriptase PCR to stage pN0 colorectal cancer patients
Expert Rev Mol Diagn. 2009 Nov;9(8) :777-85
PMID: 19895223    PMCID: PMC2810399    URL: https://www.ncbi.nlm.nih.gov/pubmed/19895223
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The most important prognostic marker of survival and predictive marker of response to adjuvant chemotherapy in colon cancer patients is tumor cells in regional lymph nodes. Despite their importance, standard techniques to assess nodal metastases remain imperfect, as approximately 30% of patients with histology-negative lymph nodes (pN0) die of recurrent disease, reflecting occult metastases that escape detection. These observations highlight the clinical need for novel, accurate approaches to detect occult lymph node metastases in patients with colon cancer. GUCY2C is a biomarker whose expression normally is restricted to intestinal cells, but is near universally overexpressed by colorectal cancer cells. Recently, a prospective, multicenter, blinded clinical trial demonstrated for the first time that the prognostic utility of GUCY2C quantitative reverse transcriptase (qRT)-PCR to detect occult lymph node metastases in pN0 colorectal cancer patients. Molecular staging revealed that approximately 13% of pN0 patients were free of tumor cells, while approximately 87% had GUCY2C results that suggested occult metastases. The presence of occult lymph node metastases was the strongest independent predictor of time to recurrence and disease-free survival. These observations establish the utility of molecular detection of occult lymph node metastases for estimating prognostic risk in pN0 colorectal cancer patients. Advancing this molecular diagnostic 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.
Mejia, Alex Schulz, Stephanie Hyslop, Terry Weinberg, David S Waldman, Scott A eng R21 CA112147/CA/NCI NIH HHS/ R01 CA075123-02/CA/NCI NIH HHS/ R01 CA095026-02/CA/NCI NIH HHS/ R01 CA075123-04/CA/NCI NIH HHS/ R01 CA075123-07/CA/NCI NIH HHS/ R01 CA095026-03/CA/NCI NIH HHS/ T32 GM008562-13/GM/NIGMS NIH HHS/ K30 RR022299-10/RR/NCRR NIH HHS/ K30 RR022299-08/RR/NCRR NIH HHS/ R01 CA095026-04/CA/NCI NIH HHS/ R01 CA095026/CA/NCI NIH HHS/ CA95026/CA/NCI NIH HHS/ R01 CA075123-06/CA/NCI NIH HHS/ R01 CA095026-06/CA/NCI NIH HHS/ K30 RR022299-09/RR/NCRR NIH HHS/ T32 GM008562-14/GM/NIGMS NIH HHS/ CA75123/CA/NCI NIH HHS/ K30 RR022299/RR/NCRR NIH HHS/ R01 CA075123-03A1/CA/NCI NIH HHS/ T32 GM08562/GM/NIGMS NIH HHS/ R01 CA075123-05/CA/NCI NIH HHS/ R01 CA095026-01A2/CA/NCI NIH HHS/ T32 GM008562/GM/NIGMS NIH HHS/ R01 CA095026-05/CA/NCI NIH HHS/ R01 CA075123/CA/NCI NIH HHS/ T32 GM008562-15/GM/NIGMS NIH HHS/ R33 CA112147/CA/NCI NIH HHS/ K30 HL004522/HL/NHLBI NIH HHS/ CA112147/CA/NCI NIH HHS/ Clinical Trial Multicenter Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England Expert Rev Mol Diagn. 2009 Nov;9(8):777-85. doi: 10.1586/erm.09.67.