Original Article(s)
Vol. 12 (2024)
Prognostic evaluation of KRAS and BRAF mutations in relation to mismatch repair protein status: preliminary survival analysis of patients with colorectal cancer
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Received: 29 December 2023
Accepted: 25 January 2024
Accepted: 25 January 2024
2927
Views
984
Downloads
Authors
Aims. Prognostic impact of mutations in BRAF and KRAS genes in patients with colorectal cancer was evaluated to detect variations in survival among patients with these mutations, in relation to different morphologic features identified at diagnosis and the expression of mismatch repair proteins. The final purpose of the project will be to establish models to predict variations in survival in different subsets of patients with colorectal cancer. Materials and Methods. Partial survival analyses were conducted on 32 subjects in relation to three different variables: mutation in BRAF or KRAS genes, expression of mismatch repair system and morphological features of the tumor. Results. Preliminary results of this study provide evidence that survival in different subsets of patients with colorectal cancer can be influenced by several factors, which include, in addition to immunohistochemical and molecular investigations, the assessment of different morphological features. Conclusions. Integrating different characteristics may reveal which factors have a more significant impact on survival in these subgroups. More patients will be needed to design different survival models and to check these preliminary results more effectively.
Downloads
Download data is not yet available.
Citations
Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA: A Cancer Journal for Clinicians. 2011;61:69-90.
Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71:209-49.
Wang W, Kandimalla R, Huang H, et al. Molecular subtyping of colorectal cancer: Recent progress, new challenges and emerging opportunities. Semin Cancer Biol. 2019;55:37-52.
Müller MF, Ibrahim AE, Arends MJ. Molecular pathological classification of colorectal cancer. Virchows Arch. 2016;469:125-34.
Munkholm P. Review article: the incidence and prevalence of colorectal cancer in inflammatory bowel disease. Aliment Pharmacol Ther. 2003;18:1-5.
Tariq K, Ghias K. Colorectal cancer carcinogenesis: a review of mechanisms. Cancer Biol Med. 2016;13:120-35.
Pino MS, Chung DC. The chromosomal instability pathway in colon cancer. Gastroenterology. 2010;138:2059-72.
Pfuderer PL, Ballhausen A, Seidler F, et al. High endothelial venules are associated with microsatellite instability, hereditary background and immune evasion in colorectal cancer. Br J Cancer. 2019;121:395-404.
Leclerc J, Vermaut C, Buisine MP. Diagnosis of Lynch Syndrome and Strategies to Distinguish Lynch-Related Tumors from Sporadic MSI/dMMR Tumors. Cancers (Basel). 2021;13:467.
Taieb J, Le Malicot K, Shi Q, et al. Prognostic Value of BRAF and KRAS Mutations in MSI and MSS Stage III Colon Cancer. J Natl Cancer Inst. 2016;109:djw272.
Formica V, Sera F, Cremolini C, et al. KRAS and BRAF Mutations in Stage II and III Colon Cancer: A Systematic Review and Meta-Analysis. J Natl Cancer Inst. 2022;114:517-27.
Boeckx N, Peeters M, Van Camp G, et al. Prognostic and Predictive Value of RAS Gene Mutations in Colorectal Cancer: Moving Beyond KRAS Exon 2. Drugs. 2015;75:1739-56.
Roth AD, Tejpar S, Delorenzi M, et al. Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial. J Clin Oncol. 2010;28:466-74.
Blons H, Emile JF, Le Malicot K, et al. Prognostic value of KRAS mutations in stage III colon cancer: post hoc analysis of the PETACC8 phase III trial dataset. Ann Oncol. 2014;25:2378-85.
Lièvre A, Bachet JB, Boige V, et al. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol. 2008;26:374-9.
Montagut C, Settleman J. Targeting the RAF-MEK-ERK pathway in cancer therapy. Cancer Lett. 2009;283:125-34.
Tejpar S, Bertagnolli M, Bosman F, et al. Prognostic and predictive biomarkers in resected colon cancer: current status and future perspectives for integrating genomics into biomarker discovery. Oncologist. 2010;15:390-404.
Sinicrope FA, Shi Q, Allegra CJ, et al. Association of DNA Mismatch Repair and Mutations in BRAF and KRAS With Survival After Recurrence in Stage III Colon Cancers : A Secondary Analysis of 2 Randomized Clinical Trials. JAMA Oncol. 2017;3:472-80.
Midthun L, Shaheen S, Deisch J, et al. Concomitant KRAS and BRAF mutations in colorectal cancer. J Gastrointest Oncol. 2019;10:577-81.
Fishel R. Mismatch repair. J Biol Chem. 2015;290:26395-403.
De' Angelis GL, Bottarelli L, Azzoni C, et al. Microsatellite instability in colorectal cancer. Acta Biomed. 2018;89:97-101.
Normanno N, Tejpar S, Morgillo F, et al. Implications for KRAS status and EGFR-targeted therapies in metastatic CRC. Nat Rev Clin Oncol. 2009;6:519-27.
Avruch J, Khokhlatchev A, Kyriakis JM, et al. Ras activation of the Raf kinase: tyrosine kinase recruitment of the MAP kinase cascade. Recent Progress in Hormone Research. 2001;56:127-55.
Kudryavtseva AV, Lipatova AV, Zaretsky AR, et al. Important molecular genetic markers of colorectal cancer. Oncotarget. 2016;7:53959-83.
Barras D. BRAF Mutation in Colorectal Cancer: An Update. Biomark Cancer. 2015;7:9-12.
Tran B, Kopetz S, Tie J, et al. Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer. Cancer. 2011;117:4623-32.
Souglakos J, Philips J, Wang R, et al. Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancer. Br J Cancer. 2009;101:465-72.
Lian SY, Tan LX, Liu XZ, et al. KRAS, NRAS, BRAF signatures, and MMR status in colorectal cancer patients in North China. Medicine (Baltimore). 2023;102:e33115.
Formica V, Sera F, Cremolini C, et al. KRAS and BRAF Mutations in Stage II and III Colon Cancer: A Systematic Review and Meta-Analysis. J Natl Cancer Inst. 2022;114:517-27. 30. Ganesh K, Stadler ZK, Cercek A, et al. Immunotherapy in colorectal cancer: rationale, challenges and potential. Nat Rev Gastroenterol Hepatol. 2019;16:361-75.
Ueno H, Price AB, Wilkinson KH, et al. A new prognostic staging system for rectal cancer. Ann Surg. 2004;240:832-9.
Karlberg M, Stenstedt K, Hallström M, et al. Tumor Budding Versus Mismatch Repair Status in Colorectal Cancer - An Exploratory Analysis. Anticancer Res. 2018;38:4713-21.
Neugut AI, Lin A, Raab GT, et al. FOLFOX and FOLFIRI Use in Stage IV Colon Cancer: Analysis of SEER- Medicare Data. Clin Colorectal Cancer. 2019;18:133-40.
Lichtenstern CR, Ngu RK, Shalapour S, Karin M. Immunotherapy, Inflammation and Colorectal Cancer. Cells. 2020;9:618.
Zugazagoitia J, Guedes C, Ponce S, et al. Current Challenges in Cancer Treatment. Clin Ther. 2016;38:1551-66.
How to Cite
Prognostic evaluation of KRAS and BRAF mutations in relation to mismatch repair protein status: preliminary survival analysis of patients with colorectal cancer. (2024). Working Paper of Public Health, 12(1). https://doi.org/10.4081/wpph.2024.9921
Copyright (c) 2024 Carlotta Bertolina, Marinella Bertolotti, Antonella Cassinari, Riccardo Mazzucco, Carolina Pelazza, Marta Betti, Antonio Maconi
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Most read articles by the same author(s)
- Paola Toselli, Roberta Di Matteo, Cesare Bolla, Barbara Montanari, Marco Ricci, Elisabeth Marino, Serena Penpa, Tatiana Bolgeo, Antonio Maconi, Evaluation of the appropriateness of control measures related to nosocomial transmission of multidrug-resistant microorganisms within the SS Multipurpose Intensive Care Unit: observational study , Working Paper of Public Health: Vol. 12 (2024)
- Roberta Di Matteo, Claudia Gota, Claudia Bina, Lorenzo Martino, Rossana Perciante, Giovanna Condino, Simona Arcidiacono, Menada Gardalini, Antonella Cassinari, Tatiana Bolgeo, Antonio Maconi, Assessment of the adequacy of bowel preparation in patients undergoing colonoscopy: a retrospective study , Working Paper of Public Health: Vol. 12 (2024)
- Alida Cotroneo, Federico Modeo, Carmelo Bennici, Roberta Di Matteo, Marinella Bertolotti, Tatiana Bolgeo, Antonio Maconi, INFORTUNI SUL LAVORO: analisi dei dati dell’Azienda Ospedaliera SS Antonio e Biagio e C. Arrigo , Working Paper of Public Health: Quaderni 2022
- Carlo Alboreo, Roberta Di Matteo, Gianluigi Piazzolla, Lucia Di Nardo, Giuseppe Dipaola, Enkeleda Gjini, Emanuele Tatò, Alessandro Scelzi, Antonio Maconi, Tatiana Bolgeo, Federico Ruta, Implementation and impact of Fast-track in an Emergency Room: pre-post study , Working Paper of Public Health: Vol. 12 (2024)
- Roberta Di Matteo, Menada Gardalini, Denise Gatti, Tatiana Bolgeo, Antonio Maconi, An investigation on nurses’ competencies and practices regarding enteral tube medication administration: a cross-sectional study , Working Paper of Public Health: Vol. 12 (2024)
- Giorgia Piceni, Gabriel Corbo, Carolina Pelazza, Serena Penpa, Marta Betti, Antonio Maconi, Data managers and clinical research coordinators: a tool to collect the hourly activity , Working Paper of Public Health: Vol. 12 (2024)
- Elisabetta Scomparin, Roberta Di Matteo, Valentina Bigucci, Valentina Repetto, Haymanot Bonelli, Erika Berta, Tatiana Bolgeo, Antonio Maconi, Contextual analysis of the first SARS-CoV-2 RNA screening period in nasopharyngeal swabs, 2020-2022: a comparison of two diagnostic tests , Working Paper of Public Health: Vol. 12 (2024)
- Daniele D'Alessio, Rossella Sterpone, Antonio Pepoli, Antonio Maconi, Intervention with strategic metacognitive training in a population of elders with subjective cognitive decline , Working Paper of Public Health: Vol. 12 (2024)
- Alessia Francese, Andrea Di Stasio, Armando Serao, Roberta Di Matteo, Mariasilvia Como, Mariateresa Dacquino, Tatiana Bolgeo, Antonio Maconi, A survey on prostate symptoms and quality of life in men with comorbidities at the Public Hospital SS. Antonio e Biagio e Cesare Arrigo of Alessandria , Working Paper of Public Health: Vol. 12 (2024)
- Valentina Manfredi, Rossella Sterpone, Antonella Cassinari, Marta Betti, Monica Franscini, Marinella Bertolotti, Simona Giribone, Antonio Pepoli, Patrizia Valorio, Carolina Pelazza, Antonio Maconi, Long-term psychological effects of COVID-19 pandemic in hospital workers in a North Italian Hospital , Working Paper of Public Health: Vol. 11 (2023)
