BACKGROUND: Mutations in the KRAS gene occur at an early stage in the development of colorectal carcinoma. Importantly, KRAS mutation predicts resistance to anti-epidermal growth factor receptor therapy in stage IV disease. GOALS: The aim of the current study is to correlate histologic features of colon cancer with the presence of KRAS mutations. STUDY: Tumor tissue from 145 colon cancer resections was tested for KRAS mutations. KRAS mutation status was correlated with demographic and histologic characteristics. Statistical analysis was performed using the Pearson χ2 test and multivariate analysis. RESULTS: KRAS mutations were present in 55/145 cases (37.9%), consistent with reported rates. KRAS mutations were significantly associated with usual adenocarcinoma morphology (multivariate P=0.014), peritumoral lymphocytic response (χ2, P=0.028; multivariate P=0.017), T3-T4 status (χ2, P=0.012; multivariate P=0.015), right-sided location (multivariate P=0.027), absence of lymphovascular invasion (multivariate P=0.008), and metastases at the time of resection (multivariate P=0.034). No association was found between KRAS mutation status and other factors. CONCLUSIONS: Specific morphologic features in colon cancer suggest a higher likelihood of the presence of KRAS mutations. These morphologic features overlap partially with those associated with DNA mismatch repair gene mutations. If confirmed, these results may suggest a paradigm for directed KRAS testing.
BACKGROUND: Mutations in the KRAS gene occur at an early stage in the development of colorectal carcinoma. Importantly, KRAS mutation predicts resistance to anti-epidermal growth factor receptor therapy in stage IV disease. GOALS: The aim of the current study is to correlate histologic features of colon cancer with the presence of KRAS mutations. STUDY: Tumor tissue from 145 colon cancer resections was tested for KRAS mutations. KRAS mutation status was correlated with demographic and histologic characteristics. Statistical analysis was performed using the Pearson χ2 test and multivariate analysis. RESULTS:KRAS mutations were present in 55/145 cases (37.9%), consistent with reported rates. KRAS mutations were significantly associated with usual adenocarcinoma morphology (multivariate P=0.014), peritumoral lymphocytic response (χ2, P=0.028; multivariate P=0.017), T3-T4 status (χ2, P=0.012; multivariate P=0.015), right-sided location (multivariate P=0.027), absence of lymphovascular invasion (multivariate P=0.008), and metastases at the time of resection (multivariate P=0.034). No association was found between KRAS mutation status and other factors. CONCLUSIONS: Specific morphologic features in colon cancer suggest a higher likelihood of the presence of KRAS mutations. These morphologic features overlap partially with those associated with DNA mismatch repair gene mutations. If confirmed, these results may suggest a paradigm for directed KRAS testing.
Authors: Rory F Kokelaar; Huw G Jones; Jeremy Williamson; Namor Williams; A Paul Griffiths; John Beynon; Gareth J Jenkins; Dean A Harris Journal: Cancer Biol Ther Date: 2018-01-19 Impact factor: 4.742
Authors: Swati Sonal; Vikram Deshpande; David T Ting; James C Cusack; Aparna R Parikh; Azfar Neyaz; Amaya Pankaj; Martin S Taylor; Anne M Dinaux; Lieve G J Leijssen; Chloe Boudreau; Joseph J Locascio; Hiroko Kunitake; Robert N Goldstone; Liliana G Bordeianou; Christy E Cauley; Rocco Ricciardi; David L Berger Journal: Ann Surg Oncol Date: 2022-08-02 Impact factor: 4.339
Authors: Niek Hugen; Michiel Simons; Altuna Halilović; Rachel S van der Post; Anna J Bogers; Monica Aj Marijnissen-van Zanten; Johannes Hw de Wilt; Iris D Nagtegaal Journal: J Pathol Clin Res Date: 2014-11-05
Authors: Jeremy Stuart Williamson; Huw Geraint Jones; Namor Williams; Anthony Paul Griffiths; Gareth Jenkins; John Beynon; Dean Anthony Harris Journal: World J Gastrointest Oncol Date: 2017-05-15