Is Tumor Testing Efficiency for Lynch Syndrome Different in Rectal and Colon Cancer? - PubMed

Is Tumor Testing Efficiency for Lynch Syndrome Different in Rectal and Colon Cancer? - PubMed

Is Tumor Testing Efficiency for Lynch Syndrome Different in Rectal and Colon Cancer?

Monica Marabelli 1, Sara Gandini 2, Paola Raviele Rafaniello 3, Mariarosaria Calvello 4, Gianluca Tolva 1, Irene Feroce 1, Matteo Lazzeroni 1, Elena Marino 5, Matteo Dal Molin 5, Cristina Trovato 6, Aliana Guerrieri-Gonzaga 1, Wanda Luisa Petz 7, Massimo Barberis 3, Lucio Bertario 1, Bernardo Bonanni 1

Affiliations 

• PMID: 32620519
 
• DOI: 10.1016/j.dld.2020.06.002

Abstract

Background: Tumor testing utility in Lynch syndrome (LS) diagnosis is established.

Aims: Analyze the differences between tumor testing efficiency in rectal (RC) and colon cancer (CC).

Methods: We performed immunohistochemistry (IHC) for MisMatch Repair (MMR) proteins (IHC-MMR) and MicroSatellite Instability analysis (MSI) on 482 unselected primary tumors: 320 CCs and 162 RCs. Samples had proficient-IHC, deficient-IHC or borderline-IHC ("patchy" expression). MSI-H borderline-IHC tumors were considered as likely MMR-deficient. Germline testing was offered to MMR-deficient patients without BRAF mutation or MLH1 promoter hypermetilation (MLH1-Hy).

Results: We identified 51/482 (10.6%) MMR-defective tumors. Multivariable analysis demonstrated a significant correlation between tumor testing results with histotype, lymph-node involvement and tumor location. In particular, RC showed a lower MMR-deficiency rate than CC (p<0.0001). Interestingly, MLH1 loss was detected in 0% RCs and 76.1% CCs, with 80% of them showing BRAF mutation/MLH1-Hy. A germline variant was detected in 12 out of 18 patients (mutation detection rate of 66.7%).

Conclusion: Tumor testing results showed molecular differences between CCs and RCs, in terms of MMR proteins expression, and presence of BRAF mutation/MLH1-Hy. MSH6 variants were the most frequent ones (50%). Although young age at diagnosis was associated with mutation detection (p = 0.045), 33.3% of LS patients were >50 years.

Keywords: Immunohistochemistry (IHC) for MisMatch Repair (MMR) proteins; Lynch syndrome; MicroSatellite Instability analysis (MSI); Tumor testing.

Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Conflict of interest statement

Conflict of interest None declared.

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