The prognostic significance of K-ras, p53, and APC mutations in colorectal carcinoma

Conlin, A.; Smith, G.; Carey, F. A.; Wolf, C. R.; Steele, R. J. C.
September 2005
Gut;Sep2005, Vol. 54 Issue 9, p1283
Academic Journal
Background: Accumulation of molecular alterations, including mutations in Kirsten-ras (K-ras), p53, and adenomatous polyposis coli (APC), contribute to colorectal carcinogenesis. Our group has previously characterised a panel of sporadic colorectal adenocarcinomas for mutations in these three genes and has shown that p53 and K-ras mutations rarely occur in the same colorectal tumour. This suggests that mutations in these genes are on separate pathways to colorectal cancer development and may influence patient prognosis independently. Aims: To correlate the presence or absence of mutations in K-ras, p53, and ARC with survival in a cohort of colorectal cancer patients. Patients: A series of 107 inpatients treated surgically for colorectal cancer in Tayside, Scotland between November 1997 and December 1999. Methods: Colorectal tumours were characterised for mutations in K-ras, p53, and ARC. Kaplan-Meier survival curves were constructed using overall survival and disease specific survival as the primary end points. Patient survival was analysed using the log rank test and Cox proportional hazards model. Results: Patients with K-ras mutations had significantly poorer overall survival than patients without K-ras mutations (p = 0.0098). Multivariate analysis correcting for Dukes' stage, age, and sex confirmed this (hazard ratio 2.9 (95% confidence interval 1.4-6.2); p = 0.0040). K-ras mutations were also significantly associated with poorer disease specific survival. The presence of APC and p53 mutations did not affect survival in this cohort of patients (p =0.9034 and p = 0.8290, respectively). Conclusions: Our data indicate that the presence of K-ras mutations predicts poor patient prognosis in colorectal cancer, independently of tumour stage.


Related Articles

  • Distinct gene expression profiles of proximal and distal colorectal cancer: implications for cytotoxic and targeted therapy. Maus, M K H; Hanna, D L; Stephens, C L; Astrow, S H; Yang, D; Grimminger, P P; Loupakis, F; Hsiang, J H; Zeger, G; Wakatsuki, T; Barzi, A; Lenz, H-J // Pharmacogenomics Journal;Aug2015, Vol. 15 Issue 4, p354 

    Colorectal cancer (CRC) is a heterogeneous disease with genetic profiles and clinical outcomes dependent on the anatomic location of the primary tumor. How location has an impact on the molecular makeup of a tumor and how prognostic and predictive biomarkers differ between proximal versus distal...

  • The BRAF mutation is associated with the prognosis in colorectal cancer. Ahn, Tae; Jeong, Dongjun; Son, Myoung; Jung, Haeil; Park, Soyoung; Kim, Hyungjoo; Bae, Sang; Kim, Han; Jeon, Young-Woo; Lee, Moon; Baek, Moo-Jun // Journal of Cancer Research & Clinical Oncology;Nov2014, Vol. 140 Issue 11, p1863 

    Background: Two members of the Ras/Raf signaling pathway, KRAS and B-raf, are suspected to be involved in the stepwise progression of colorectal cancer (CRC) tumorigenesis. Objective: We compared the KRAS and BRAF mutation status of CRC patients with their clinicopathological characteristics and...

  • Prognostic value of hedgehog signaling pathway in patients with colon cancer. Xu, Meihua; Li, Xinhua; Liu, Ting; Leng, Aimin; Zhang, Guiying // Medical Oncology;Jun2012, Vol. 29 Issue 2, p1010 

    Hedgehog signaling pathway plays an important role in normal mammalian gastrointestinal development and is implicated in the oncogenesis of various tumors. However, its correlation with progression and prognosis of colon cancer has not been well documented. This study was designed to investigate...

  • Novel recurrently mutated genes and a prognostic mutation signature in colorectal cancer. Jun Yu; Wu, William K. K.; Xiangchun Li; Jun He; Xiao-Xing Li; Ng, Simon S. M.; Chang Yu; Zhibo Gao; Jie Yang; Miao Li; Qiaoxiu Wang; Qiaoyi Liang; Yi Pan; Tong, Joanna H.; To, Ka F.; Nathalie Wong; Ning Zhang; Jie Chen; Youyong Lu; Lai, Paul B. S // Gut;Apr2015, Vol. 64 Issue 4, p636 

    Background Characterisation of colorectal cancer (CRC) genomes by next-generation sequencing has led to the discovery of novel recurrently mutated genes. Nevertheless, genomic data has not yet been used for CRC prognostication. Objective To identify recurrent somatic mutations with prognostic...

  • Distal and proximal colon cancers differ in terms of molecular, pathological, and clinical features. Missiaglia, E.; Jacobs, B.; D'Ario, G.; Di Narzo, A. F.; Soneson, C.; Budinska, E.; Popovici, V.; Vecchione, L.; Gerster, S.; Yan, P.; Roth, A. D.; Klingbiel, D.; Bosman, F. T.; Delorenzi, M.; Tejpar, S. // Annals of Oncology;Oct2014, Vol. 25 Issue 10, p1995 

    Our study supports the notion that tumors arising in the distal or proximal colon develop along different tumorigenic pathways, leading to carcinomas with unique characteristics, showing differences in prognosis and response to targeted therapy.Background Differences exist between the proximal...

  • P-0288BRAF MUTATION IN COLON CANCER PATIENTS WITH MICROSATELLITE INSTABILITY (MSI): A MONOINSTITUTIONAL ANALYSIS. Frisinghelli, Michela; Veccia, Antonello; Soini, Barbara; Brugnara, Sonia; Russo, Lucianna Maria; Barbareschi, Mattia; Togni, Roberto; Girlando, Salvatore; Galligioni, Enzo // Annals of Oncology;Jun2013, Vol. 24 Issue suppl_4, piv116 

    No abstract available.

  • High BRAF Mutation Frequency and Marked Survival Differences in Subgroups According to KRAS/BRAF Mutation Status and Tumor Tissue Availability in a Prospective Population-Based Metastatic Colorectal Cancer Cohort. Sorbye, Halfdan; Dragomir, Anca; Sundström, Magnus; Pfeiffer, Per; Thunberg, Ulf; Bergfors, Monica; Aasebø, Kristine; Eide, Geir Egil; Ponten, Fredrik; Qvortrup, Camilla; Glimelius, Bengt // PLoS ONE;Jun2015, Vol. 10 Issue 6, p1 

    RAS and BRAF mutations impact treatment and prognosis of metastatic colorectal cancer patients (mCRC), but the knowledge is based on trial patients usually not representative for the general cancer population. Patient characteristics, treatment and efficacy according to KRAS, BRAF and MSI status...

  • RAD21 cohesin overexpression is a prognostic and predictive marker exacerbating poor prognosis in KRAS mutant colorectal carcinomas. Deb, S; Xu, H; Tuynman, J; George, J; Yan, Y; Li, J; Ward, R L; Mortensen, N; Hawkins, N J; McKay, M J; Ramsay, R G; Fox, S B // British Journal of Cancer;3/11/2014, Vol. 110 Issue 6, p1606 

    Background:RAD21 is a component of the cohesion complex and is integral to chromosome segregation and error-free DNA repair. RAD21 is functionally important in tumour progression but its role in colorectal carcinoma (CRC) is unclear. We therefore assessed its clinicopathological and prognostic...

  • KRAS developments and implementation of findings. Kelley, Robin K.; Venook, Alan P. // Hem/Onc Today;9/10/2008, Vol. 9 Issue 16, p3 

    The author discusses the developments in the study of the tumor Kirsten ras (KRAS) gene mutational status. He states that around 30% to 50% of colorectal cancer specimens hold a mutation in the KRAS gene. He admits that there is no clear reason about the results from CAIRO2 that diverge from the...


Read the Article


Sign out of this library

Other Topics