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KRAS mutation and microsatellite instability: two genetic markers of early tumor development that influence the prognosis of colorectal cancer.


ABSTRACT: 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.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.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.MSI and KRAS mutation provide fundamental genetic signatures influencing tumor behavior across patient subsets and stages of tumor development.

SUBMITTER: Nash GM 

PROVIDER: S-EPMC4380015 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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KRAS mutation and microsatellite instability: two genetic markers of early tumor development that influence the prognosis of colorectal cancer.

Nash Garrett M GM   Gimbel Mark M   Cohen Alfred M AM   Zeng Zhao-Shi ZS   Ndubuisi Mackevin I MI   Nathanson Daniel R DR   Ott Jurg J   Barany Francis F   Paty Philip B PB  

Annals of surgical oncology 20091008 2


<h4>Introduction</h4>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.<h4>Patients and methods</h4>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 sur  ...[more]

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