title: Occult tumor burden predicts disease recurrence in lymph node-negative colorectal cancer.
abstract: OBJECTIVE
  Lymph node involvement by histopathology informs colorectal cancer prognosis, whereas recurrence in 25% of node-negative patients suggests the presence of occult metastasis. GUCY2C (guanylyl cyclase C) is a marker of colorectal cancer cells that identifies occult nodal metastases associated with recurrence risk. Here, we defined the association of occult tumor burden, quantified by GUCY2C reverse transcriptase-PCR (RT-PCR), with outcomes in colorectal cancer.
  
  
  METHODS
  Lymph nodes (range: 2-159) from 291 prospectively enrolled node-negative colorectal cancer patients were analyzed by histopathology and GUCY2C quantitative RT-PCR. Participants were followed for a median of 24 months (range: 2-63). Time to recurrence and disease-free survival served as primary and secondary outcomes, respectively. Association of outcomes with prognostic markers, including molecular tumor burden, was estimated by recursive partitioning and Cox models.
  
  
  RESULTS
  In this cohort, 176 (60%) patients exhibited low tumor burden (Mol(Low)), and all but four remained free of disease [recurrence rate 2.3% (95% CI, 0.1-4.5%)]. Also, 90 (31%) patients exhibited intermediate tumor burden (Mol(Int)) and 30 [33.3% (23.7-44.1)] developed recurrent disease. Furthermore, 25 (9%) patients exhibited high tumor burden (Mol(High)) and 17 [68.0% (46.5-85.1)] developed recurrent disease (P < 0.001). Occult tumor burden was an independent marker of prognosis. Mol(Int) and Mol(High) patients exhibited a graded risk of earlier time to recurrence [Mol(Int), adjusted HR 25.52 (11.08-143.18); P < 0.001; Mol(High), 65.38 (39.01-676.94); P < 0.001] and reduced disease-free survival [Mol(Int), 9.77 (6.26-87.26); P < 0.001; Mol(High), 22.97 (21.59-316.16); P < 0.001].
  
  
  CONCLUSIONS
  Molecular tumor burden in lymph nodes is independently associated with time to recurrence and disease-free survival in patients with node-negative colorectal cancer.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Terry
authors.initials: T
authors.lastname: Hyslop
authors.forename: David S
authors.initials: DS
authors.lastname: Weinberg
authors.forename: Stephanie
authors.initials: S
authors.lastname: Schulz
authors.forename: Alan
authors.initials: A
authors.lastname: Barkun
authors.forename: Scott A
authors.initials: SA
authors.lastname: Waldman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D018000:Receptors, Peptide / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D012008:Recurrence; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D018000:Receptors, Peptide; C000613654:GUCY2C protein, human; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled