KRAS mutation and microsatellite instability: Two genetic markers of early tumor development that influence the prognosis of colorectal cancer Journal Article


Authors: Nash, G. M.; Gimbel, M.; Cohen, A. M.; Zeng, Z. S.; Ndubuisi, M. I.; Nathanson, D. R.; Ott, J.; Barany, F.; Paty, P. B.
Article Title: KRAS mutation and microsatellite instability: Two genetic markers of early tumor development that influence the prognosis of colorectal cancer
Abstract: Introduction: We examined two genetic markers established early in colorectal tumor development, microsatellite instability (MSI) and mutation of the KRAS proto-oncogene, to see if these genetic changes influence metastatic disease progression and survival. Patients and methods: MSI and KRAS mutation status were assessed in 532 primary adenocarcinomas (stage I-IV) from patients treated by colon resection. Median follow-up was 4.1 years (range 0-13.3 years) overall, 5.4 years for survivors. Results: MSI and KRAS mutation were detected in 12 and 36% of cases, respectively. MSI was more common in early-stage disease (I, 15%; II, 21%; III, 10%; IV, 2%; P = 0.0001). Prevalence of KRAS mutation did not vary with stage (I, 36%; II, 34%; III, 35%; IV, 40%; P = ns). Disease-specific survival was far superior for MSI tumors than for microsatellite stability (MSS) tumors (5-year survival 92 vs. 59%, P < 0.0001). KRAS mutation was a marker of poor survival (5-year survival 55 vs. 68%, P = 0.0002). Using Cox regression analysis MSI, KRAS mutation, and stage were strong independent predictors of survival in the entire patient population. A high-mortality group with MSS/KRAS-mutant tumors was identified within the stage I and II cohort. Conclusions: MSI and KRAS mutation provide fundamental genetic signatures influencing tumor behavior across patient subsets and stages of tumor development. © 2009 Society of Surgical Oncology.
Keywords: adult; cancer survival; controlled study; human tissue; treatment outcome; aged; aged, 80 and over; middle aged; survival rate; young adult; gene mutation; major clinical study; mutation; proto-oncogene proteins; cancer growth; cancer adjuvant therapy; cancer staging; follow up; follow-up studies; colorectal cancer; adenocarcinoma; proto oncogene; cancer mortality; carcinogenesis; colorectal neoplasms; survival time; early cancer; disease progression; microsatellite instability; colon resection; ras proteins; oncogene k ras; colon; genetic marker; genetic markers; rectum
Journal Title: Annals of Surgical Oncology
Volume: 17
Issue: 2
ISSN: 1068-9265
Publisher: Springer  
Date Published: 2010-02-01
Start Page: 416
End Page: 424
Language: English
DOI: 10.1245/s10434-009-0713-0
PUBMED: 19813061
PROVIDER: scopus
PMCID: PMC4380015
DOI/URL:
Notes: --- - "Cited By (since 1996): 2" - "Export Date: 20 April 2011" - "CODEN: ASONF" - "Source: Scopus"
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MSK Authors
  1. Mark I Gimbel
    14 Gimbel
  2. Philip B Paty
    380 Paty
  3. Zhaoshi Zeng
    86 Zeng
  4. Garrett Nash
    141 Nash