Scientific publications

Clinical and Pathological Characterization of Lynch-Like Syndrome

Feb 1, 2022 | Magazine: Clinical Gastroenterology and Hepatology

María Dolores Picó  1 , Adela Castillejo  2 , Óscar Murcia  3 , Mar Giner-Calabuig  3 , Miren Alustiza  3 , Ariadna Sánchez  4 , Leticia Moreira  4 , María Pellise  4 , Antoni Castells  4 , Marta Carrillo-Palau  5 , Teresa Ramon Y Cajal  6 , Alexandra Gisbert-Beamud  6 , Gemma Llort  7 , Carmen Yagüe  7 , Adriá López-Fernández  8 , Cristina Alvarez-Urturi  9 , Joaquin Cubiella  10 , Laura Rivas  10 , Daniel Rodríguez-Alcalde  11 , Maite Herraiz  12 , Catalina Garau  13 , Carlos Dolz  13 , Luis Bujanda  14 , Lucia Cid  15 , Carmen Povés  16 , Marta Garzon  17 , Inmaculada Salces  18 , Marta Ponce  19 , Luís Hernández-Villalba  20 , Cristina Alenda  21 , Francesc Balaguer  4 , Jose-Luis Soto  2 , Rodrigo Jover  22

Background & aims: Lynch syndrome is characterized by DNA mismatch repair (MMR) deficiency. Some patients with suspected Lynch syndrome have DNA MMR deficiencies but no detectable mutations in genes that encode MMR proteins-this is called Lynch-like syndrome (LLS). There is no consensus on management of patients with LLS. We collected data from a large series of patients with LLS to identify clinical and pathology features.

Methods: We collected data from a nationwide-registry of patients with colorectal cancer (CRC) in Spain. We identified patients whose colorectal tumors had loss of MSH2, MSH6, PMS2, or MLH1 (based on immunohistochemistry), without the mutation encoding V600E in BRAF (detected by real-time PCR), and/or no methylation at MLH1 (determined by methylation-specific multiplex ligation-dependent probe amplification), and no pathogenic mutations in MMR genes, BRAF, or EPCAM (determined by DNA sequencing). These patients were considered to have LLS. We collected data on demographic, clinical, and pathology features and family history of neoplasms. The χ2 test was used to analyze the association between qualitative variables, followed by the Fisher exact test and the Student t test or the Mann-Whitney test for quantitative variables.

Results: We identified 160 patients with LLS; their mean age at diagnosis of CRC was 55 years and 66 patients were female (41%). The Amsterdam I and II criteria for Lynch syndrome were fulfilled by 11% of cases and the revised Bethesda guideline criteria by 65% of cases. Of the patients with LLS, 24% were identified in universal screening. There were no proportional differences in sex, indication for colonoscopy, immunohistochemistry, pathology findings, or personal history of CRC or other Lynch syndrome-related tumors between patients who met the Amsterdam and/or Bethesda criteria for Lynch syndrome and patients identified in universal screening for Lynch syndrome, without a family history of CRC.

Conclusions: Patients with LLS have homogeneous clinical, demographic, and pathology characteristics, regardless of family history of CRC.

CITATION Clin Gastroenterol Hepatol. 2020 Feb;18(2):368-374.e1.  doi: 10.1016/j.cgh.2019.06.012. Epub 2019 Jun 17.

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