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. 2023 Nov;26(6):958-968.
doi: 10.1007/s10120-023-01411-3. Epub 2023 Jun 29.

Concordance of microsatellite instability and mismatch repair status in paired biopsies and surgical specimens of resectable gastroesophageal adenocarcinoma: time for a call to action

Lorenzo Fornaro #  1 , Sara Lonardi #  2 , Silvia Catanese  3   4 , Floriana Nappo  2 , Filippo Pietrantonio  5 , Antonio Pellino  6 , Valentina Angerilli  7 , Francesca Signorini  8 , Francesca Salani  3   9 , Sabina Murgioni  2 , Ioana Ancuta Neculaescu  7 , Rossella Bruno  10 , Caterina Vivaldi  3   11 , Gianmarco Ricagno  2   12 , Gianluca Masi  3   11 , Francesca Bergamo  2 , Clara Ugolini #  8 , Matteo Fassan #  2   7
Affiliations

Concordance of microsatellite instability and mismatch repair status in paired biopsies and surgical specimens of resectable gastroesophageal adenocarcinoma: time for a call to action

Lorenzo Fornaro et al. Gastric Cancer. 2023 Nov.

Abstract

Background: Reliability of mismatch repair proteins and microsatellite instability assessment is essential in order to define treatment strategy and identify candidates to immune checkpoint inhibitors in locally advanced gastroesophageal carcinoma. We evaluated the concordance of deficient mismatch repair (dMMR) and microsatellite instability-high (MSI-H) status between endoscopic biopsies and surgical specimens.

Methods: Consecutive patients with resectable gastric or gastroesophageal junction adenocarcinoma classified as MSI-H/dMMR by polymerase chain reaction (PCR) or immunohistochemistry (IHC) and operated at three referral Institutions were included. The primary endpoint was the rate of concordance between biopsy and surgical samples. If needed, central revision by IHC/PCR was performed by specialized pathologists from coordinating Institutions.

Results: Thirteen (19.7%) out of 66 patients showed discordant MSI-H/dMMR results in the original pathology reports. In most cases (11, 16.7%) this was due to the diagnosis of proficient mismatch repair status on biopsies. Among the ten cases available for central review, four were due to sample issues, four were reclassified as dMMR, one case showed dMMR status but was classified as microsatellite stable by PCR, one was linked to misdiagnosis of endoscopic biopsy by the local pathologist. Heterogeneity of mismatch repair proteins staining was observed in two cases.

Conclusions: Available methods can lead to conflicting results in MSI-H/dMMR evaluation between endoscopic biopsies and surgical samples of gastroesophageal adenocarcinoma. Strategies aiming to improve the reliability of assessment should be primarily focused on the optimization of tissue collection and management during endoscopy and adequate training of dedicated gastrointestinal pathologists within the multidisciplinary team.

Keywords: DNA mismatch repair complex; Gastric adenocarcinoma; Gastroesophageal junction adenocarcinoma; Microsatellite instability; Mismatch repair proteins.

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References

    1. Smyth EC, Nilsson M, Grabsch HI, van Grieken NC, Lordick F. Gastric cancer. Lancet. 2020;396:635–48. https://doi.org/10.1016/S0140-6736(20)31288-5 . - DOI - PubMed
    1. Fornaro L, Vasile E, Aprile G, Goetze TO, Vivaldi C, Falcone A, Al-Batran SE. Locally advanced gastro-oesophageal cancer: recent therapeutic advances and research directions. Cancer Treat Rev. 2018;69:90–100. https://doi.org/10.1016/j.ctrv.2018.06.012 . - DOI - PubMed
    1. Reynolds JV, Preston SR, O’Neill B, Lowery MA, Baeksgaard L, Crosby T, et al. Neo-AEGIS (Neoadjuvant Trial in Adenocarcinoma of the Esophagus and Esophago-Gastric Junction International Study): final primary outcome analysis. J Clin Oncol. 2023;41(suppl 4):295–295. https://doi.org/10.1200/JCO.2023.41.4_suppl.295 . - DOI
    1. Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet. 2019;393:1948–57. https://doi.org/10.1016/S0140-6736(18)32557-1 . - DOI - PubMed
    1. Han S, Chok AY, Peh DYY, Ho JZ, Tan EKW, Koo SL, et al. The distinct clinical trajectory, metastatic sites, and immunobiology of microsatellite-instability-high cancers. Front Genet. 2022;13:933475. https://doi.org/10.3389/fgene.2022.933475 . - DOI - PubMed - PMC

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