Influence of Microsatellite Instability and KRAS and BRAF Mutations on Lymph Node Harvest in Stage I–III Colon Cancers
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 BRAFV600E 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.
This study was funded in part by grants from the Folke Hermansens Cancer Foundation (grant 424508 to K Søreide for M Berg as a postdoctoral fellow) and the Mjaaland Cancer Research Fund (grant 424506 to K Søreide). This work was also supported in part by grants from the Norwegian Cancer Society (grants 2008-0151 to RA Lothe for TC Ahlquist as a postdoctoral fellow, 2009-0231 to RA Lothe and T-97452 to O Nordgård) and from the Western Norway Health authorities (grant 911115 to O Nordgård). TC Ahlquist is currently employed by Roche Norway.
- 20.Pallant J. (2010) Multiple regression. In: SPSS Survival Manual. McGraw-Hill, London, pp. 146–67.Google Scholar
- 21.Lang TA, Secic M.(2006) Prediciting values from one or more variables: reporting regression analyses. In: How to Report Statistics in Medicine. Annotated Guidelines for Authors, Editors, and Reviewers. Lang TA, Secic M, Eds. American College of Physicians, Philadelphia, pp. 85–107.Google Scholar
- 23.Morikawa T, et al. (2012) Predictors of lymph node count in colorectal cancer resections: data from US nationwide prospective cohort studies. Arch. Surg. 8:715–23.Google Scholar
- 27.MacQuarrie E, et al. (2012) Microsatellite instability status does not predict total lymph node or negative lymph node retrieval in stage III colon cancer. Hum. Pathol. 43:1256–64.Google Scholar
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