Oncotarget

Research Papers:

Advantage of HSP110 (T17) marker inclusion for microsatellite instability (MSI) detection in colorectal cancer patients

Gustavo Noriz Berardinelli, Cristovam Scapulatempo-Neto, Ronílson Durães, Marco Antônio de Oliveira, Denise Guimarães and Rui Manuel Reis _

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Oncotarget. 2018; 9:28691-28701. https://doi.org/10.18632/oncotarget.25611

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Abstract

Gustavo Noriz Berardinelli1, Cristovam Scapulatempo-Neto1, Ronílson Durães1,2, Marco Antônio de Oliveira3, Denise Guimarães1,4 and Rui Manuel Reis1,5,6

1Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil

2Department of Oncology, Barretos Cancer Hospital, Jales, São Paulo, Brazil

3Nucleus of Epidemiology and Biostatistics, Barretos Cancer Hospital, Barretos, São Paulo, Brazil

4Department of Endoscopy, Barretos Cancer Hospital, Barretos, São Paulo, Brazil

5Life and Health sciences Research Institute, University of Minho, Gualtar Campus, Braga, Portugal

6ICVS/3B’s-PT Government Associate Laboratory, Gualtar Campus, Braga, Portugal

Correspondence to:

Rui Manuel Reis, email: ruireis.hcb@gmail.com

Keywords: colorectal cancer; microsatellite instability; molecular diagnostic; immunohistochemistry; HSP110 (T17)

Received: November 02, 2017    Accepted: April 04, 2018    Published: June 19, 2018

ABSTRACT

Colorectal cancer (CRC) is a leading cause of cancer death worldwide. Microsatellite instability (MSI) is a genetic pathway leading to CRC, associated with particular clinicopathological features, and recently a major biomarker of immunotherapy response. There is little information the frequency MSI among Brazilian CRC patients, and it is still debatable the ideal methodology for MSI screening in countries with limited resources. We proposed to evaluate MSI by molecular and immunohistochemistry (IHC) methods, to compare both methodologies and also to assess the inclusion of a novel microsatellite marker, HSP110 (T17). The molecular MSI evaluation was performed using a PCR-multiplex panel in a total of 1013 CRC patients. Mismatch repair (MMR) proteins (MLH1, MSH2, MSH6 and PMS2) expression were evaluated by IHC. HSP110 (T17) marker was analyzed by fragment analysis. Molecularly, 89.5% of cases were MSI-negative and 10.5% were MSI-positive. The IHC showed that 88.9% of cases exhibited MMR-proficient status, 10.2% were MMR-deficient and 0.9% was inconclusive. Genotyping of the HSP110 (T17) in 106 MSI-positive and 215 MSI-negative cases showed its alteration only among the MSI-positive cases. We observed agreement (0.956, Kappa Test) between both molecular and IHC methodologies, with only eight discordant results, and in this subset of cases the HSP110 (T17) corroborate the molecular findings. This study suggests the use of molecular assays over IHC for MSI analysis and proposes the inclusion HSP110 (T17) marker as a complementary analysis in discordant cases.


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