Is tumor testing efficiency for Lynch syndrome different in rectal and colon cancer?

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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.

Original languageEnglish
Pages (from-to)1503-1511
Number of pages9
JournalDigestive and Liver Disease
Issue number12
Publication statusPublished - Dec 2020


  • Immunohistochemistry (IHC) for MisMatch Repair (MMR) proteins
  • Lynch syndrome
  • MicroSatellite Instability analysis (MSI)
  • Tumor testing

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology


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