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- 2019-10-11 (2)
- 2019-10-11 (1)
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Palabras clave
Carcinoma
inestabilidad microsatelital
inmunohistoquímica para MMR
agregación familiar carcinoma
Microsatelite Instability
immunohistochemistry for MMRs
inestabilidad microsatelital
inmunohistoquímica para MMR
agregación familiar carcinoma
Microsatelite Instability
immunohistochemistry for MMRs
Cómo citar
Bohórquez, M. E., Criollo, Ángel A., Carvajal Carmona, L., & Echeverry de Polanco, M. M. (2019). Cáncer de colon en Colombia, fenotipo molecular: tamizaje para síndromes con agregación familiar. REVISTA DE LA ASOCIACION COLOMBIANA DE CIENCIAS BIOLOGICAS, 1(31), 87–99. https://doi.org/10.47499/revistaaccb.v1i31.185
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.
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2. 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.
---------------------------------------------------------------------------------------------------
3. Fearon ER. (2011) Molecular genetics of colorectal cancer. Annu Rev Pathol.;6:479-507.
---------------------------------------------------------------------------------------------------
4. Kastrinos F, Syngal S. Inherited colorectal cancer syndromes. (2011) Cancer J. 17(6):405-15.
---------------------------------------------------------------------------------------------------
5. Stoffel EM, Kastrinos F. (2014) Familial colorectal cancer, beyond Lynch syndrome. Clin Gastroenterol Hepatol. 12(7):1059-68.
---------------------------------------------------------------------------------------------------
6. Armelao F, de Pretis G. (2014) Familial colorectal cancer: a review. World J Gastroenterol. 20(28):9292-8.
---------------------------------------------------------------------------------------------------
7. 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.
---------------------------------------------------------------------------------------------------
8. Bedeir A, Krasinskas AM. (2011) Molecular diagnostics of colorectal cancer. Arch Pathol Lab Med. 135(5):578-87.
---------------------------------------------------------------------------------------------------
9. Boland CR, Goel A. (2010) Microsatellite instability in colorectal cancer. Gastroenterology. 138(6):2073-87 e3.
---------------------------------------------------------------------------------------------------
10. 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.
---------------------------------------------------------------------------------------------------
11. Laurent-Puig P, Agostini J, Maley K. (2010) [Colorectal oncogenesis]. Bulletin du cancer. 97(11):1311-21.
---------------------------------------------------------------------------------------------------
12. 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.
---------------------------------------------------------------------------------------------------
13. Bolocan A, Ion D, Ciocan DN, Paduraru DN. (2012) Prognostic and predictive factors in colorectal cancer. Chirurgia (Bucur). 107(5):555-63.
---------------------------------------------------------------------------------------------------
14. 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.
---------------------------------------------------------------------------------------------------
15. 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.
---------------------------------------------------------------------------------------------------
16. 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.
---------------------------------------------------------------------------------------------------
17. 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.
---------------------------------------------------------------------------------------------------
18. Ritterhouse LL, Barletta JA. (2015) BRAF V600E mutation-specifi c antibody: A review. Semin Diagn Pathol. 32(5):400-8.
---------------------------------------------------------------------------------------------------
19. 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.
---------------------------------------------------------------------------------------------------
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