Versiones
- 2019-10-11 (2)
- 2019-10-11 (1)
##plugins.themes.healthSciences.article.supplementaryFiles##
Palabras clave
inestabilidad microsatelital
inmunohistoquímica para MMR
agregación familiar carcinoma
Microsatelite Instability
immunohistochemistry for MMRs
Cómo citar
Resumen
Objetivo: Caracterizar las características clínico-patológicas y algunos fenotipos moleculares del cáncer colorrectal (CCR), en 1278 pacientes de la región andina colombiana.
Métodos: Se analizó una muestra de 1278 pacientes con CCR. Análisis de expresión de los genes MMR-Mismatch Repair-hMLH1, utilizando métodos inmunohistoquímicos (IHC). Para inestabilidad microsatelital-MSI se utilizó ADN de tejido tumoral-normal mediante PCR.
Resultados: Promedio de edad 57,4 años, la enfermedad es más frecuente en el género femenino 53,2%. La frecuencia de pacientes menores de 50 años (26,5%) es mayor a la esperada, el CCR en estos casos se asoció a tipos histológicos agresivos -carcinoma mucinoso y carcinoma en anillo de sello- p=<0,000, los cuales, a su vez, resultaron asociados a inestabilidad microsatelital (MSI-H). La localización más frecuente: recto (31,1%), p=0,002, el diagnóstico se produjo en estados avanzados de la enfermedad T3-T4 (75,1%) p=0,022. Tipo histológico más frecuente: adenocarcinoma. La sensibilidad del análisis inmunohistoquímico de MLH1 para la detección de MSI+, fue de 71% (CI: 49 - 87). El análisis por IHC-MLH1 en 575 casos mostró pérdida de la expresión en el 7% de los pacientes. Las pruebas de MSI se realizaron en 451 casos de CCR; el 23% presentaron alta inestabilidad microsatelital (MSI-H).
Conclusión: La determinación de inestabilidad microsatelital y la inmunohistoquímica para MMR permiten identificar pacientes en riesgo de ser portadores de mutaciones relacionadas con síndrome de Lynch en pacientes colombianos.
Citas
IARC IAFROC. GLOBOCAN_2018: WHO; 2018 Consultado de: http://gco.iarc.fr/today/home.
---------------------------------------------------------------------------------------------------
Binefa G, Rodriguez-Moranta F, Teule A, Medina-Hayas M. (2014) Colorectal cancer: from prevention to personalized medicine. World J Gastroenterol. 20(22):6786-808.
---------------------------------------------------------------------------------------------------
Fearon ER. (2011) Molecular genetics of colorectal cancer. Annu Rev Pathol.;6:479-507.
---------------------------------------------------------------------------------------------------
Kastrinos F, Syngal S. Inherited colorectal cancer syndromes. (2011) Cancer J. 17(6):405-15.
---------------------------------------------------------------------------------------------------
Stoffel EM, Kastrinos F. (2014) Familial colorectal cancer, beyond Lynch syndrome. Clin Gastroenterol Hepatol. 12(7):1059-68.
---------------------------------------------------------------------------------------------------
Armelao F, de Pretis G. (2014) Familial colorectal cancer: a review. World J Gastroenterol. 20(28):9292-8.
---------------------------------------------------------------------------------------------------
Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, et al. (1998). A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res. 58(22):5248-57.
---------------------------------------------------------------------------------------------------
Bedeir A, Krasinskas AM. (2011) Molecular diagnostics of colorectal cancer. Arch Pathol Lab Med. 135(5):578-87.
---------------------------------------------------------------------------------------------------
Boland CR, Goel A. (2010) Microsatellite instability in colorectal cancer. Gastroenterology. 138(6):2073-87 e3.
---------------------------------------------------------------------------------------------------
Yashiro M, Hirakawa K, Boland CR. (2010) Mutations in TGFbeta-RII and BAX mediate tumor progression in the later stages of colorectal cancer with microsatellite instability. BMC cancer. 10:303.
---------------------------------------------------------------------------------------------------
Laurent-Puig P, Agostini J, Maley K. (2010) [Colorectal oncogenesis]. Bulletin du cancer. 97(11):1311-21.
---------------------------------------------------------------------------------------------------
Shima K, Morikawa T, Yamauchi M, Kuchiba A, Imamura Y, Liao X, et al. (2011) TGFBR2 and BAX mononucleotide tract mutations, microsatellite instability, and prognosis in 1072 colorectal cancers. PLoS One. 6(9): e25062.
---------------------------------------------------------------------------------------------------
Bolocan A, Ion D, Ciocan DN, Paduraru DN. (2012) Prognostic and predictive factors in colorectal cancer. Chirurgia (Bucur). 107(5):555-63.
---------------------------------------------------------------------------------------------------
Kloor M, Staffa L, Ahadova A, von Knebel Doeberitz M. (2014) Clinical signifi cance of microsatellite instability in colorectal cancer. Langenbeck’s archives of surgery / Deutsche Gesellschaft fur Chirurgie. 399(1):23-31.
---------------------------------------------------------------------------------------------------
Levidou G, Saetta AA, Gigelou F, Karlou M, Papanastasiou P, Stamatelli A, et al. (2012) ERK/pERK expression and B-raf mutations in colon adenocarcinomas: correlation with clinicopathological characteristics. World J Surg Oncol. 10:47.
---------------------------------------------------------------------------------------------------
Qin J, Xie P, Ventocilla C, Zhou G, Vultur A, Chen Q, et al. (2012) Identifi cation of a novel family of BRAF(V600E) inhibitors. J Med Chem.;55(11):5220-30.
---------------------------------------------------------------------------------------------------
Chen D, Huang JF, Liu K, Zhang LQ, Yang Z, Chuai ZR, et al. (2014) BRAFV600E mutation and its association with clinicopathological features of colorectal cancer: a systematic review and metaanalysis. PLoS One. 9(3): e90607.
---------------------------------------------------------------------------------------------------
Ritterhouse LL, Barletta JA. (2015) BRAF V600E mutation-specifi c antibody: A review. Semin Diagn Pathol. 32(5):400-8.
---------------------------------------------------------------------------------------------------
Kalady MF, Dejulius KL, Sanchez JA, Jarrar A, Liu X, Manilich E, et al. (2012) BRAF mutations in colorectal cancer are associated with distinct clinical characteristics and worse prognosis. Dis Colon Rectum. 55(2):128-33.
---------------------------------------------------------------------------------------------------
Pritchard CC, Grady WM. (2011) Colorectal cancer molecular biology moves into clinical practice. Gut. 60(1):116-29.
---------------------------------------------------------------------------------------------------
Murcia O, Juarez M, Hernandez-Illan E, Egoavil C, Giner-Calabuig M, Rodriguez-Soler M, et al. (2016) Serrated colorectal cancer: Molecular classifi cation, prognosis, and response to chemotherapy. World J Gastroenterol. 22(13):3516-30.
---------------------------------------------------------------------------------------------------
QIAGEN. QIAGEN KIT, Dneasy – Blood & Tissue Kit. 2013.
---------------------------------------------------------------------------------------------------
Thermo-Fisher S. 2013 Consultado de: http://www.nanodrop.com/Products.aspx
---------------------------------------------------------------------------------------------------
Ghazi S, Berg E, Lindblom A, Lindforss U. (2013) Clinicopathological analysis of colorectal cancer: a comparison between emergency and elective surgical cases. World J Surg Oncol. 11:133.
---------------------------------------------------------------------------------------------------
Domingo E, Ramamoorthy R, Oukrif D, Rosmarin D, Presz M, Wang H, et al. (2013) Use of multivariate analysis to suggest a new molecular classifi cation of colorectal cancer. J pathol 229(3):441-8.
---------------------------------------------------------------------------------------------------
McKay A, Donaleshen J, Helewa RM, Park J, Wirtzfeld D, Hochman D, et al. (2014) Does young age influence the prognosis of colorectal cancer: a population-based analysis. World J Surg Oncol. 12:370.
---------------------------------------------------------------------------------------------------
Millan M, Merino S, Caro A, Feliu F, Escuder J, Francesch T. (2015) Treatment of colorectal cancer in the elderly. World J Gastrointest Oncol. 7(10):204-20.
---------------------------------------------------------------------------------------------------
Dodou D, de Winter JC. (2012) The relationship between distal and proximal colonic neoplasia: a meta-analysis. J Gen Intern Med. 27(3):361-70.
---------------------------------------------------------------------------------------------------
Hansen IO, Jess P. (2012) Possible better long-term survival in left versus right-sided colon cancer - a systematic review. Dan Med J. 59(6): A4444.
---------------------------------------------------------------------------------------------------
Purim O, Gordon N, Brenner B. (2013) Cancer of the colon and rectum: potential effects of sex-age interactions on incidence and outcome. Med Sci Monit. 19:203-9.
---------------------------------------------------------------------------------------------------
Wu QJ, Vogtmann E, Zhang W, Xie L, Yang WS, Tan YT, et al. (2012) Cancer incidence among adolescents and young adults in urban Shanghai, 1973-2005. PLoS One. 7(8): e42607.
---------------------------------------------------------------------------------------------------
Brenner H, Kloor M, Pox CP. (2014) Colorectal cancer. Lancet. 383(9927):1490-502.
---------------------------------------------------------------------------------------------------
Karanikas M, Esebidis A. (2016) Increasing incidence of colon cancer in patients <50 years old: a new entity? Ann Transl Med. 4(9):164.
---------------------------------------------------------------------------------------------------
Fedewa SA, Ma J, Sauer AG, Siegel RL, Smith RA, Wender RC, et al. (2015) How many individuals will need to be screened to increase colorectal cancer screening prevalence to 80% by 2018? Cancer. 121(23):4258-65.
---------------------------------------------------------------------------------------------------
Deschoolmeester V, Boeckx C, Baay M, Weyler J, Wuyts W, Van Marck E, et al. (2010) KRAS mutation detection and prognostic potential in sporadic colorectal cancer using high-resolution melting analysis. Br J Cancer. 103(10):1627-36.
---------------------------------------------------------------------------------------------------
Krivokapic Z, Markovic S, Antic J, Dimitrijevic I, Bojic D, Svorcan P, et al. (2012) Clinical and pathological tools for identifying microsatellite instability in colorectal cancer. Croat Med J. 53(4):328-35.
---------------------------------------------------------------------------------------------------
Raskin L, Dakubo JC, Palaski N, Greenson JK, Gruber SB. (2013) Distinct molecular features of colorectal cancer in Ghana. Cancer Epidemiol. 37(5):556-61.
---------------------------------------------------------------------------------------------------
Sorbye H, Dragomir A, Sundstrom M, Pfeiffer P, Thunberg U, Bergfors M, et al. (2015) 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. PLoS One. 10(6): e0131046.
---------------------------------------------------------------------------------------------------
Ogino S, Goel A. (2008) Molecular classifi cation and correlates in colorectal cancer. J mol diagn. 10(1):13-27.
---------------------------------------------------------------------------------------------------
Nazemalhosseini Mojarad E, Kashfi SM, Mirtalebi H, Taleghani MY, Azimzadeh P, Savabkar S, et al. (2016) Low Level of Microsatellite Instability Correlates with Poor Clinical Prognosis in Stage II Colorectal Cancer Patients. J Oncol. 2016:2196703.
---------------------------------------------------------------------------------------------------
Greenson JK, Huang SC, Herron C, Moreno V, Bonner JD, Tomsho LP, et al. (2009) Pathologic predictors of microsatellite instability in colorectal cancer. Am J Surg Pathol. 33(1):126-33.
---------------------------------------------------------------------------------------------------
Ashktorab H, Ahuja S, Kannan L, Llor X, Ellis NA, Xicola RM, et al. (2016) A meta-analysis of MSI frequency and race in colorectal cancer. Oncotarget. 7(23):34546-34557.
---------------------------------------------------------------------------------------------------
Gupta S, Ashfaq R, Kapur P, Afonso BB, Nguyen TP, Ansari F, et al. (2010) Microsatellite instability among individuals of Hispanic origin with colorectal cancer. Cancer. 116(21):4965-4972.
---------------------------------------------------------------------------------------------------
Batur S, Vuralli Bakkaloglu D, Kepil N, Erdamar S. (2016) Microsatellite instability and BRAF mutation in colorectal cancer: clinicopathological characteristics and effects on survival. Bosn J Basic Med Sci.16(4):254-260.
---------------------------------------------------------------------------------------------------
Kanth VV, Bhalsing S, Sasikala M, Rao GV, Pradeep R, Avanthi US, et al. (2014) Microsatellite instability and promoter hypermethylation in colorectal cancer in India. Tumour biol: 35(5):4347-4355.
---------------------------------------------------------------------------------------------------
Kamat N, Khidhir MA, Alashari MM, Rannug U. (2013) Microsatellite instability and loss of heterozygosity detected in middle-aged patients with sporadic colon cancer: A retrospective study. Oncol Lett. 6(5):1413-1420.
---------------------------------------------------------------------------------------------------
Shia J, Ellis NA, Paty PB, Nash GM, Qin J, Offi t K, et al. (2003) Value of histopathology in predicting microsatellite instability in hereditary nonpolyposis colorectal cancer and sporadic colorectal cancer. Am J Surg Pathol. 27(11):1407-1417.
---------------------------------------------------------------------------------------------------
Hall G, Clarkson A, Shi A, Langford E, Leung H, Eckstein RP, et al. (2010) Immunohistochemistry for PMS2 and MSH6 alone can replace a four antibody panel for mismatch repair defi ciency screening in colorectal adenocarcinoma. Pathology. 42(5):409-13.
---------------------------------------------------------------------------------------------------
Raut CP, Pawlik TM, Rodriguez-Bigas MA. (2004) Clinicopathologic features in colorectal cancer patients with microsatellite instability. Mutat Res. 568(2):275-82.
---------------------------------------------------------------------------------------------------
Jung SH, Kim SH, Kim JH. (2016) Prognostic impact of microsatellite instability in colorectal cancer presenting with mucinous, signet-ring, and poorly differentiated cells. Ann Coloproctol. 32(2):58-65.
---------------------------------------------------------------------------------------------------
Kaya M, Basak F, Sisik A, Hasbahceci M, Bas G, Alimoglu O, et al. (2017) Validation of microsatellite instability histology scores with Bethesda guidelines in hereditary nonpolyposis colorectal cancer. J Cancer Res Ther. 13(2):356-61.
---------------------------------------------------------------------------------------------------
Vakiani E. (2017) Molecular Testing of Colorectal Cancer in the Modern Era: What Are We Doing and Why? Surg pathol clin. 10(4):1009-20.
---------------------------------------------------------------------------------------------------
Alqahtani M, Grieu F, Carrello A, Amanuel B, Mashour M, Alattas R, et al. (2016) Screening for Lynch Syndrome in young colorectal cancer patients from Saudi Arabia using microsatellite instability as the initial test. Asian Pac J Cancer Prev. 17(4):1917-23.
---------------------------------------------------------------------------------------------------
Setaffy L, Langner C. (2015) Microsatellite instability in colorectal cancer: clinicopathological significance. Pol J Pathol. 66(3):203-18.
---------------------------------------------------------------------------------------------------
Boissiere-Michot F, Frugier H, Ho-Pun-Cheung A, Lopez-Crapez E, Duffour J, Bibeau F. (2016) Immunohistochemical staining for p16 and BRAFV600E is useful to distinguish between sporadic and hereditary (Lynch syndrome-related) microsatellite instable colorectal carcinomas. Virchows Arch.
(2):135-44.
---------------------------------------------------------------------------------------------------
Shamekh R, Cives MM, J, Coppola D. (2016) Higher frequency of isolated PMS2 loss in colorectal tumors in Colombian population: preliminary results. Pathol Lab Med Intern. 8:37-41
---------------------------------------------------------------------------------------------------
Ortiz C, Dongo-Pfl ucker K, Martin-Cruz L, Barletta Carrillo C, Mora-Alferez P, Arias A. (2016) Microsatellite instability in patients with diagnostic of colorectal cancer. Rev Gastroenterol Peru. 36(1):15-22.
---------------------------------------------------------------------------------------------------
5Gatalica Z, Vranic S, Xiu J, Swensen J, Reddy S. (2016) High microsatellite instability (MSI-H) colorectal carcinoma: a brief review of predictive biomarkers in the era of personalized medicine. Fam Cancer. 15(3):405-12.
---------------------------------------------------------------------------------------------------
Kim IY. (2016) Impact of microsatellite instability in signet-ring cell and mucinous components in patients with colorectal carcinoma. Ann Coloproctol. 32(2):45-6.
---------------------------------------------------------------------------------------------------
Kudryavtseva AV, Lipatova AV, Zaretsky AR, Moskalev AA, Fedorova MS, Rasskazova AS, et al. (2016) Important molecular genetic markers of colorectal cancer. Oncotarget. 16;7(33):53959-83.
---------------------------------------------------------------------------------------------------
Siddique S, Tariq K, Rafi q S, Raheem A, Ahmed R, Shabbir-Moosajee M, et al. (2016) Sporadic Early Onset Colorectal Cancer in Pakistan: A Case- Control Analysis of Microsatellite Instability. Asian Pac J Cancer Prev.;17(5):2587-92.
---------------------------------------------------------------------------------------------------
Shia J, Klimstra DS, Nafa K, Offi t K, Guillem JG, Markowitz AJ, et al. (2005) Value of immunohistochemical detection of DNA mismatch repair proteins in predicting germline mutation in hereditary colorectal neoplasms. Am J Surg Pathol.;29(1):96-104.
---------------------------------------------------------------------------------------------------
Becouarn Y, Rullier A, Gorry P, Smith D, Richard-Molard B, Echinard E, et al. (2005) Value of microsatellite instability typing in detecting hereditary non-polyposis colorectal cancer. A prospective multicentric study by the Association Aquitaine Gastro. Gastroenterol Clin Biol. 29(6-7):667-75.
---------------------------------------------------------------------------------------------------
Shia J. (2008) Immunohistochemistry versus microsatellite instability testing for screening colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome. Part I. The utility of immunohistochemistry. J Mol Diagn. 10(4):293-300.
---------------------------------------------------------------------------------------------------
Shia J, Tang LH, Vakiani E, Guillem JG, Stadler ZK, Soslow RA, et al. (2009) Immunohistochemistry as fi rst-line screening for detecting colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome: a 2-antibody panel may be as predictive as a 4-antibody panel. Am J Surg
Pathol. 33(11):1639-45.
---------------------------------------------------------------------------------------------------
Niessen RC, Berends MJ, Wu Y, Sijmons RH, Hollema H, Ligtenberg MJ, et al. (2006) Identifi cation of mismatch repair gene mutations in young patients with colorectal cancer and in patients with multiple tumours associated with hereditary non-polyposis colorectal cancer. Gut. 55(12):1781-8.
---------------------------------------------------------------------------------------------------
Hendriks Y, Franken P, Dierssen JW, De Leeuw W, Wijnen J, Dreef E, et al. (2003) Conventional and tissue microarray immunohistochemical expression analysis of mismatch repair in hereditary colorectal tumors. Am J Pathol.;162(2):469-77.
---------------------------------------------------------------------------------------------------
Luevano-Gonzalez A, Guzman AQ, Ancer Rodriguez J, Ortiz Lopez R, Rojas Martinez A, Gonzalez Guerrero JF, et al. (2011) Analysis of DNA mismatch repair proteins expression and BRAF V600E mutation in a subset of early- and late-onset colorectal carcinoma patients in Mexico. Arch Med Res. 42(6):457-62.
---------------------------------------------------------------------------------------------------
Waldmann E, Ferlitsch M, Binder N, Sellner F, Karner J, Heinisch B, et al. (2015) Tumor and Patient Characteristics of Individuals with Mismatch Repair Defi cient Colorectal Cancer. Digestion. 91(4):286-93.
---------------------------------------------------------------------------------------------------
Sekal M, Ameurtesse H, Chbani L, Ouldim K, Bennis S, Abkari M, et al. (2015) Epigenetics could explain some Moroccan population colorectal cancers peculiarities: microsatellite instability pathway exploration. Diagn Pathol.;10:77.
---------------------------------------------------------------------------------------------------
Colling R, Church DN, Carmichael J, Murphy L, East J, Risby P, et al. (2015) Screening for Lynch syndrome and referral to clinical genetics by selective mismatch repair protein immunohistochemistry testing: an audit and cost analysis. J Clin Pathol. 68(12):1036-9.
---------------------------------------------------------------------------------------------------
South CD, Yearsley M, Martin E, Arnold M, Frankel W, Hampel H. (2009) Immunohistochemistry staining for the mismatch repair proteins in the clinical care of patients with colorectal cancer. Genet med. 11(11):812-7.
---------------------------------------------------------------------------------------------------
Sawada T, Yamamoto E, Yamano HO, Nojima M, Harada T, Maruyama R, et al. (2016) Assessment of epigenetic alterations in early colorectal lesions containing BRAF mutations. Oncotarget. 7(23):35106-18.
---------------------------------------------------------------------------------------------------
Bae JM, Kim JH, Kang GH. (2016) Molecular Subtypes of Colorectal Cancer and Their Clinicopathologic Features, With an emphasis on the serrated neoplasia pathway. Arch Pathol Lab Med. 140(5):406-12.
---------------------------------------------------------------------------------------------------
Jia M, Gao X, Zhang Y, Hoffmeister M, Brenner H. (2016) Different defi nitions of CpG island methylator phenotype and outcomes of colorectal cancer: a systematic review. Clin Epigenetics. 8:25.
---------------------------------------------------------------------------------------------------
Duraturo F, Liccardo R, Cavallo A, De Rosa M, Rossi GB, Izzo P. (2015) Multivariate analysis as a method for evaluating the pathogenicity of novel genetic MLH1 variants in patients with colorectal cancer and microsatellite instability. Int J Mol Med. 36(2):511-7.
---------------------------------------------------------------------------------------------------
Samowitz WS, Sweeney C, Herrick J, Albertsen H, Levin TR, Murtaugh MA, et al. (2005) Poor survival associated with the BRAF V600E mutation in microsatellite-stable colon cancers. Cancer Res. 65(14):6063-9.
---------------------------------------------------------------------------------------------------
Li WQ, Kawakami K, Ruszkiewicz A, Bennett G, Moore J, Iacopetta B. (2006) BRAF mutations are associated with distinctive clinical, pathological and molecular features of colorectal cancer independently of microsatellite instability status. Mol Cancer. 5:2.
---------------------------------------------------------------------------------------------------
Lubomierski N, Plotz G, Wormek M, Engels K, Kriener S, Trojan J, et al. (2005) BRAF mutations in colorectal carcinoma suggest two entities of microsatellite-unstable tumors. Cancer. 104(5):952-61.
---------------------------------------------------------------------------------------------------
Marzouk O, Schofi eld J. (2011) Review of histopathological and molecular prognostic features in colorectal cancer. Cancers. 3(2):2767-810.
---------------------------------------------------------------------------------------------------
Sayagues JM, Del Carmen S, Del Mar Abad M, Corchete LA, Bengoechea O, Anduaga MF, et al. (2018) Combined assessment of the TNM stage and BRAF mutational status at diagnosis in sporadic colorectal cancer patients. Oncotarget. 9(35):24081-96.
---------------------------------------------------------------------------------------------------
D’Haene N, Fontanges Q, De Neve N, Blanchard O, Melendez B, Delos M, et al. (2018) Clinical application of targeted next-generation sequencing for colorectal cancer patients: a multicentric Belgian experience. Oncotarget. 9(29):20761-8.
---------------------------------------------------------------------------------------------------
Koinuma K, Shitoh K, Miyakura Y, Furukawa T, Yamashita Y, Ota J, et al. (2004) Mutations of BRAF are associated with extensive hMLH1 promoter methylation in sporadic colorectal carcinomas. Int J cancer 108(2):237-42.
---------------------------------------------------------------------------------------------------
Ye JX, Liu Y, Qin Y, Zhong HH, Yi WN, Shi XY. (2015) KRAS and BRAF gene mutations and DNA mismatch repair status in Chinese colorectal carcinoma patients. World J Gastroenterol. 21(5):1595-605.
---------------------------------------------------------------------------------------------------
Mao C, Zhou J, Yang Z, Huang Y, Wu X, Shen H, et al. (2012) KRAS, BRAF and PIK3CA mutations and the loss of PTEN expression in Chinese patients with colorectal cancer. PLoS One. 7(5): e36653.
---------------------------------------------------------------------------------------------------
Shen H, Yuan Y, Hu HG, Zhong X, Ye XX, Li MD, et al. (2011) Clinical signifi cance of K-ras and BRAF mutations in Chinese colorectal cancer patients. World J Gastroenterol. 17(6):809-16.
---------------------------------------------------------------------------------------------------
Naguib A, Mitrou PN, Gay LJ, Cooke JC, Luben RN, Ball RY, et al. (2010) Dietary, lifestyle and clinicopathological factors associated with BRAF and K-ras mutations arising in distinct subsets of colorectal cancers in the EPIC Norfolk study. BMC Cancer. 10:99.
---------------------------------------------------------------------------------------------------
Zlobec I, Bihl MP, Schwarb H, Terracciano L, Lugli A. (2010) Clinicopathological and protein characterization of BRAF- and K-RAS-mutated colorectal cancer and implications for prognosis. Int J Cancer. 127(2):367-80.
---------------------------------------------------------------------------------------------------
Shaukat A, Arain M, Thaygarajan B, Bond JH, Sawhney M. (2010) Is BRAF mutation associated with interval colorectal cancers? Dig Dis Sci. 55(8):2352-6.
---------------------------------------------------------------------------------------------------
Loupakis F, Ruzzo A, Cremolini C, Vincenzi B, Salvatore L, Santini D, et al. (2009) KRAS codon 61,146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer. Br J Cancer. 101(4):715-21.
---------------------------------------------------------------------------------------------------
Phipps AI, Buchanan DD, Makar KW, Burnett-Hartman AN, Coghill AE, Passarelli MN, et al. (2012) BRAF mutation status and survival after colorectal cancer diagnosis according to patient and tumor characteristics. Cancer Epidemiol Biomarkers Prev. 21(10):1792-8.
---------------------------------------------------------------------------------------------------
Rozek LS, Herron CM, Greenson JK, Moreno V, Capella G, Rennert G, et al. (2010) Smoking, gender, and ethnicity predict somatic BRAF mutations in colorectal cancer. Cancer Epidemiol Biomarkers Prev. 19(3):838-43.
---------------------------------------------------------------------------------------------------
Sinicrope FA, Shi Q, Smyrk TC, Thibodeau SN, Dienstmann R, Guinney J, et al. (2015) Molecular markers identify subtypes of stage III colon cancer associated with patient outcomes. Gastroenterology 148(1):88-99.
---------------------------------------------------------------------------------------------------
Thiel A, Ristimaki A. (2013) Toward a molecular classifi cation of colorectal cancer: The role of BRAF. Front Oncol 3:281.
---------------------------------------------------------------------------------------------------
Wangefjord S, Sundstrom M, Zendehrokh N, Lindquist KE, Nodin B, Jirstrom K, et al. (2013) Sex differences in the prognostic signifi cance of KRAS codons 12 and 13, and BRAF mutations in colorectal cancer: a cohort study. Biol Sex Differ. 4(1):17.
Esta obra está bajo una licencia internacional Creative Commons Atribución-CompartirIgual 4.0.
Derechos de autor 2019 REVISTA DE LA ASOCIACION COLOMBIANA DE CIENCIAS BIOLOGICAS