title: Influence of microsatellite instability and KRAS and BRAF mutations on lymph node harvest in stage I-III colon cancers.
abstract: Lymph node (LN) harvest is influenced by several factors, including tumor genetics. Microsatellite instability (MSI) is associated with improved node harvest, but the association to other genetic factors is largely unknown. Research methods included a prospective series of stage I-III colon cancer patients undergoing ex vivo sentinel-node sampling. The presence of MSI, KRAS mutations in codons 12 and 13, and BRAF V600E mutations was analyzed. Uni- and multivariate regression models for node sampling were adjusted for clinical, pathological and molecular features. Of 204 patients, 67% had an adequate harvest (≥ 12 nodes). Adequate harvest was highest in patients whose tumors exhibited MSI (79%; odds ratio [OR] 2.5, 95% confidence interval [CI] 1.2-4.9; P = 0.007) or were located in the proximal colon (73%; 2.8, 1.5-5.3; P = 0.002). In multiple linear regression, MSI was a significant predictor of the total LN count (P = 0.02). Total node count was highest for cancers with MSI and no KRAS/BRAF mutations. The independent association between MSI and a high LN count persisted for stage I and II cancers (P = 0.04). Tumor location in the proximal colon was the only significant predictor of an adequate LN harvest (adjusted OR 2.4, 95% CI 1.2-4.9; P = 0.01). An increase in the total number of nodes harvested was not associated with an increase in nodal metastasis. In conclusion, number of nodes harvested is highest for cancers of the proximal colon and with MSI. The nodal harvest associated with MSI is influenced by BRAF and KRAS genotypes, even for cancers of proximal location. Mechanisms behind the molecular diversity and node yield should be further explored.
authors: Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway.
authors: Marianne
authors: M
authors: Berg
authors: Department of Cancer Prevention, Institute for Cancer Research, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway.|Center for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors: Marianne
authors: M
authors: Guriby
authors: Department of Hematology and Oncology, Stavanger University Hospital, Stavanger, Norway.
authors: Oddmund
authors: O
authors: Nordgård
authors: Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway.
authors: Bjørn S
authors: BS
authors: Nedrebø
authors: Department of Cancer Prevention, Institute for Cancer Research, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway.|Center for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors: Terje C
authors: TC
authors: Ahlquist
authors: Department of Hematology and Oncology, Stavanger University Hospital, Stavanger, Norway.
authors: Rune
authors: R
authors: Smaaland
authors: Department of Hematology and Oncology, Stavanger University Hospital, Stavanger, Norway.
authors: Satu
authors: S
authors: Oltedal
authors: Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway.|Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors: Jon Arne
authors: JA
authors: Søreide
authors: Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway.|Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors: Hartwig
authors: H
authors: Kørner
authors: Department of Cancer Prevention, Institute for Cancer Research, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway.|Center for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors: Ragnhild A
authors: RA
authors: Lothe
authors: Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway.|Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors: Kjetil
authors: K
authors: Søreide
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D055815:Young Adult; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
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