title: Molecular staging estimates occult tumor burden in colorectal cancer.
abstract: 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 approximately 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 overexpressed 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 approximately 13% of pN0 patients were free of cancer cells, while approximately 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.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Mejia
authors.forename: Stephanie
authors.initials: S
authors.lastname: Schulz
authors.forename: Terry
authors.initials: T
authors.lastname: Hyslop
authors.forename: David S
authors.initials: DS
authors.lastname: Weinberg
authors.forename: Scott A
authors.initials: SA
authors.lastname: Waldman
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000145:classification / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D009367:Neoplasm Staging / Q000379:methods*; D011379:Prognosis; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D018000:Receptors, Peptide / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D018000:Receptors, Peptide; C000613654:GUCY2C protein, human; D006162:Guanylate Cyclase; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled