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Article

KRAS and BRAF mutations and MSI status in precursor lesions of colorectal cancer detected by colonoscopy

  • Authors:
    • L. S. Yamane
    • C. Scapulatempo-Neto
    • L. Alvarenga
    • C. Z. Oliveira
    • G. N. Berardinelli
    • E. Almodova
    • T. R. Cunha
    • G. Fava
    • W. Colaiacovo
    • A. Melani
    • J. H. Fregnani
    • R. M. Reis
    • D. P. Guimarães
  • View Affiliations / Copyright

    Affiliations: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil, Department of Pathology, Barretos Cancer Hospital, Barretos, São Paulo, Brazil, Department of Endoscopy, Barretos Cancer Hospital, Barretos, São Paulo, Brazil, Department of Epidemiology and Biostatistics, Barretos Cancer Hospital, Barretos, São Paulo, Brazil, Department of Digestive Surgery, Barretos Cancer Hospital, Barretos, São Paulo, Brazil
  • Pages: 1419-1426
    |
    Published online on: July 18, 2014
       https://doi.org/10.3892/or.2014.3338
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Abstract

Colorectal cancer (CRC) is one of the most frequent cancers worldwide. Adenoma is the main precursor lesion and, recently, the serrated polyps were described as a group of colorectal lesions with malignant potential. The morphologic and biologic characterizations of serrated polyps remain limited. The aim of the present study was to determine the frequency of KRAS and BRAF mutations and microsatellite instability (MSI) in CRC precursor lesions, to evaluate the association between molecular, pathologic and morphologic alterations in precursor lesions and to compare with the alterations detected in CRC. A series of 342 precursor lesions were removed from 155 patients during colonoscopy. After morphologic classification, molecular analysis was performed in 103 precursor lesions, and their genetic profile compared with 47 sporadic CRCs. Adenomas were the main precursor lesions (70.2%). Among the serrated polyps, the main precursor lesion was hyperplastic polyps (HPs) (82.4%), followed by sessile serrated adenomas (12.7%) and traditional serrated adenomas (2.0%). KRAS mutations were detected in 13.6% of the precursor lesions, namely in adenomas and in HPs, but in no serrated adenoma. BRAF mutations were found in 9 (8.7%) precursor lesions, mainly associated with serrated polyps and absent in adenomas (P<0.001). High MSI (MSI-H) was absent in precursor lesions. In the 47 CCR cases, 46.8% exhibited KRAS mutation, 6.5% BRAF mutations and 10.6% MSI-H. This study confirms the role of KRAS and BRAF mutations in CRC carcinogenesis, a crucial step in implementing CRC screening strategies.
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1 

Brasil. Ministério da Saúde. Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA). Coordenação Geral de Ações Estratégicas. Coordenação de Prevenção e Vigilância: Estimativa 2012: incidência de câncer no Brasil. INCA; Rio de Janeiro: 2011, (In Portuguese).

2 

Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar

3 

Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 127:2893–2917. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Goss PE, Lee BL, Badovinac-Crnjevic T, et al: Planning cancer control in Latin America and the Caribbean. Lancet Oncol. 14:391–436. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Fearon ER and Vogelstein B: A genetic model for colorectal tumorigenesis. Cell. 61:759–767. 1990. View Article : Google Scholar : PubMed/NCBI

6 

Lieberman DA, Weiss DG, Bond JH, Ahnen DJ, Garewal H and Chejfec G: Use of colonoscopy to screen asymptomatic adults for colorectal cancer. Veterans Affairs Cooperative Study Group 380. N Engl J Med. 343:162–168. 2000. View Article : Google Scholar : PubMed/NCBI

7 

Leggett B and Whitehall V: Role of the serrated pathway in colorectal cancer pathogenesis. Gastroenterology. 138:2088–2100. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Tuppurainen K, Makinen JM, Junttila O, et al: Morphology and microsatellite instability in sporadic serrated and non-serrated colorectal cancer. J Pathol. 207:285–294. 2005. View Article : Google Scholar : PubMed/NCBI

9 

Yamane L, Scapulatempo-Neto C, Reis RM and Guimarães DP: Serrated pathway in colorectal carcinogenesis. World J Gastroenterol. 20:2634–2640. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Garcia-Solano J, Perez-Guillermo M, Conesa-Zamora P, et al: Clinicopathologic study of 85 colorectal serrated adenocarcinomas: further insights into the full recognition of a new subset of colorectal carcinoma. Hum Pathol. 41:1359–1368. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Rex DK: Colonoscopic withdrawal technique is associated with adenoma miss rates. Gastrointest Endosc. 51:33–36. 2000. View Article : Google Scholar : PubMed/NCBI

12 

Imperiale TF and Ransohoff DF: Understanding differences in the guidelines for colorectal cancer screening. Gastroenterology. 138:1642–1647. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Laghi L and Malesci A: Microsatellite instability and therapeutic consequences in colorectal cancer. Dig Dis. 30:304–309. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Vilar E and Gruber SB: Microsatellite instability in colorectal cancer-the stable evidence. Nat Rev Clin Oncol. 7:153–162. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Sebolt-Leopold JS and Herrera R: Targeting the mitogen-activated protein kinase cascade to treat cancer. Nat Rev Cancer. 4:937–947. 2004. View Article : Google Scholar : PubMed/NCBI

16 

Kudo S, Lambert R, Allen JI, et al: Nonpolypoid neoplastic lesions of the colorectal mucosa. Gastrointest Endosc. 68:S3–S47. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Bosman FT, Carneiro F, Hruban RH and Theise ND: IARC WHO Classification of Tumours of the Digestive System. 4th edition. IARC Press; Lyon: 2010

18 

Valadao M, Braggio D, Santos AF, et al: Involvement of signaling molecules in the prediction of response to imatinib treatment in metastatic GIST patients. J Surg Res. 178:288–293. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Martinho O, Gouveia A, Viana-Pereira M, et al: Low frequency of MAP kinase pathway alterations in KIT and PDGFRA wild-type GISTs. Histopathology. 55:53–62. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Campanella NC, Berardinelli GN, Scapulatempo-Neto C, et al: Optimization of a pentaplex panel for MSI analysis without control DNA in a Brazilian population: correlation with ancestry markers. Eur J Hum Genet. 22:875–880. 2014. View Article : Google Scholar : PubMed/NCBI

21 

Carr NJ, Mahajan H, Tan KL, Hawkins NJ and Ward RL: Serrated and non-serrated polyps of the colorectum: their prevalence in an unselected case series and correlation of BRAF mutation analysis with the diagnosis of sessile serrated adenoma. J Clin Pathol. 62:516–518. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Bariol C, Hawkins NJ, Turner JJ, Meagher AP, Williams DB and Ward RL: Histopathological and clinical evaluation of serrated adenomas of the colon and rectum. Mod Pathol. 16:417–423. 2003. View Article : Google Scholar : PubMed/NCBI

23 

Kahi CJ, Hewett DG, Norton DL, Eckert GJ and Rex DK: Prevalence and variable detection of proximal colon serrated polyps during screening colonoscopy. Clin Gastroenterol Hepatol. 9:42–46. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Spring KJ, Zhao ZZ, Karamatic R, et al: High prevalence of sessile serrated adenomas with BRAF mutations: a prospective study of patients undergoing colonoscopy. Gastroenterology. 131:1400–1407. 2006. View Article : Google Scholar : PubMed/NCBI

25 

Iino H, Jass JR, Simms LA, et al: DNA microsatellite instability in hyperplastic polyps, serrated adenomas, and mixed polyps: a mild mutator pathway for colorectal cancer? J Clin Pathol. 52:5–9. 1999. View Article : Google Scholar : PubMed/NCBI

26 

Tadepalli US, Feihel D, Miller KM, et al: A morphologic analysis of sessile serrated polyps observed during routine colonoscopy (with video). Gastrointest Endosc. 74:1360–1368. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Mäkinen MJ: Colorectal serrated adenocarcinoma. Histopathology. 50:131–150. 2007.

28 

Groff RJ, Nash R and Ahnen DJ: Significance of serrated polyps of the colon. Curr Gastroenterol Rep. 10:490–498. 2008. View Article : Google Scholar : PubMed/NCBI

29 

Rex DK, Ahnen DJ, Baron JA, et al: Serrated lesions of the colorectum: review and recommendations from an expert panel. Am J Gastroenterol. 107:1315–1329. 2012. View Article : Google Scholar : PubMed/NCBI

30 

Winawer SJ, Zauber AG, Fletcher RH, et al: Guidelines for colonoscopy surveillance after polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society. Gastroenterology. 130:1872–1885. 2006. View Article : Google Scholar

31 

Torlakovic E and Snover DC: Serrated adenomatous polyposis in humans. Gastroenterology. 110:748–755. 1996. View Article : Google Scholar : PubMed/NCBI

32 

Torlakovic E, Skovlund E, Snover DC, Torlakovic G and Nesland JM: Morphologic reappraisal of serrated colorectal polyps. Am J Surg Pathol. 27:65–81. 2003. View Article : Google Scholar : PubMed/NCBI

33 

Yadamsuren EA, Nagy S, Pajor L, Lacza A and Bogner B: Characteristics of advanced- and non advanced sporadic polypoid colorectal adenomas: correlation to KRAS mutations. Pathol Oncol Res. 18:1077–1084. 2012. View Article : Google Scholar : PubMed/NCBI

34 

Yang S, Farraye FA, Mack C, Posnik O and O’Brien MJ: BRAF and KRAS mutations in hyperplastic polyps and serrated adenomas of the colorectum: relationship to histology and CpG island methylation status. Am J Surg Pathol. 28:1452–1459. 2004. View Article : Google Scholar : PubMed/NCBI

35 

Rad R, Cadinanos J, Rad L, et al: A genetic progression model of Braf(V600E)-induced intestinal tumorigenesis reveals targets for therapeutic intervention. Cancer Cell. 24:15–29. 2013. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yamane LS, Scapulatempo-Neto C, Alvarenga L, Oliveira CZ, Berardinelli GN, Almodova E, Cunha TR, Fava G, Colaiacovo W, Melani A, Melani A, et al: KRAS and BRAF mutations and MSI status in precursor lesions of colorectal cancer detected by colonoscopy. Oncol Rep 32: 1419-1426, 2014.
APA
Yamane, L.S., Scapulatempo-Neto, C., Alvarenga, L., Oliveira, C.Z., Berardinelli, G.N., Almodova, E. ... Guimarães, D.P. (2014). KRAS and BRAF mutations and MSI status in precursor lesions of colorectal cancer detected by colonoscopy. Oncology Reports, 32, 1419-1426. https://doi.org/10.3892/or.2014.3338
MLA
Yamane, L. S., Scapulatempo-Neto, C., Alvarenga, L., Oliveira, C. Z., Berardinelli, G. N., Almodova, E., Cunha, T. R., Fava, G., Colaiacovo, W., Melani, A., Fregnani, J. H., Reis, R. M., Guimarães, D. P."KRAS and BRAF mutations and MSI status in precursor lesions of colorectal cancer detected by colonoscopy". Oncology Reports 32.4 (2014): 1419-1426.
Chicago
Yamane, L. S., Scapulatempo-Neto, C., Alvarenga, L., Oliveira, C. Z., Berardinelli, G. N., Almodova, E., Cunha, T. R., Fava, G., Colaiacovo, W., Melani, A., Fregnani, J. H., Reis, R. M., Guimarães, D. P."KRAS and BRAF mutations and MSI status in precursor lesions of colorectal cancer detected by colonoscopy". Oncology Reports 32, no. 4 (2014): 1419-1426. https://doi.org/10.3892/or.2014.3338
Copy and paste a formatted citation
x
Spandidos Publications style
Yamane LS, Scapulatempo-Neto C, Alvarenga L, Oliveira CZ, Berardinelli GN, Almodova E, Cunha TR, Fava G, Colaiacovo W, Melani A, Melani A, et al: KRAS and BRAF mutations and MSI status in precursor lesions of colorectal cancer detected by colonoscopy. Oncol Rep 32: 1419-1426, 2014.
APA
Yamane, L.S., Scapulatempo-Neto, C., Alvarenga, L., Oliveira, C.Z., Berardinelli, G.N., Almodova, E. ... Guimarães, D.P. (2014). KRAS and BRAF mutations and MSI status in precursor lesions of colorectal cancer detected by colonoscopy. Oncology Reports, 32, 1419-1426. https://doi.org/10.3892/or.2014.3338
MLA
Yamane, L. S., Scapulatempo-Neto, C., Alvarenga, L., Oliveira, C. Z., Berardinelli, G. N., Almodova, E., Cunha, T. R., Fava, G., Colaiacovo, W., Melani, A., Fregnani, J. H., Reis, R. M., Guimarães, D. P."KRAS and BRAF mutations and MSI status in precursor lesions of colorectal cancer detected by colonoscopy". Oncology Reports 32.4 (2014): 1419-1426.
Chicago
Yamane, L. S., Scapulatempo-Neto, C., Alvarenga, L., Oliveira, C. Z., Berardinelli, G. N., Almodova, E., Cunha, T. R., Fava, G., Colaiacovo, W., Melani, A., Fregnani, J. H., Reis, R. M., Guimarães, D. P."KRAS and BRAF mutations and MSI status in precursor lesions of colorectal cancer detected by colonoscopy". Oncology Reports 32, no. 4 (2014): 1419-1426. https://doi.org/10.3892/or.2014.3338
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