Clinical and Pathological Characterization of Lynch-Like Syndrome

María Dolores Picó; Adela Castillejo; Óscar Murcia; Mar Giner-Calabuig; Miren Alustiza; Ariadna Sánchez; Leticia Moreira; María Pellise; Antoni Castells; Marta Carrillo-Palau; Teresa Ramon y Cajal; Alexandra Gisbert-Beamud; Gemma Llort; Carmen Yagüe; Adriá López-Fernández; Cristina Alvarez-Urturi; Joaquin Cubiella; Laura Rivas; Daniel Rodríguez-Alcalde; Maite Herraiz; Catalina Garau; Carlos Dolz; Luis Bujanda; Lucia Cid; Carmen Povés; Marta Garzon; Inmaculada Salces; Marta Ponce; Luís Hernández-Villalba; Cristina Alenda; Francesc Balaguer; Jose Luis Soto; Rodrigo Jover

doi:10.1016/j.cgh.2019.06.012

Clinical and Pathological Characterization of Lynch-Like Syndrome

María Dolores Picó, Adela Castillejo, Óscar Murcia, Mar Giner-Calabuig, Miren Alustiza, Ariadna Sánchez, Leticia Moreira, María Pellise, Antoni Castells, Marta Carrillo-Palau, Teresa Ramon y Cajal, Alexandra Gisbert-Beamud, Gemma Llort, Carmen Yagüe, Adriá López-Fernández, Cristina Alvarez-Urturi, Joaquin Cubiella, Laura Rivas, Daniel Rodríguez-Alcalde, Maite HerraizCatalina Garau, Carlos Dolz, Luis Bujanda, Lucia Cid, Carmen Povés, Marta Garzon, Inmaculada Salces, Marta Ponce, Luís Hernández-Villalba, Cristina Alenda, Francesc Balaguer, Jose Luis Soto, Rodrigo Jover

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	368-374.e1
Journal	Clinical Gastroenterology and Hepatology
Volume	18
Issue number	2
DOIs	https://doi.org/10.1016/j.cgh.2019.06.012
State	Published - Feb 2020

Bibliographical note

Funding Information:
Funding Supported by the Instituto de Salud Carlos III (PI08/0726, INT-09/208, PI11/2630, INT-12-078, INT13-196, PI14/01386, PI17/01756), Fundación de Investigación Biomédica de la Comunidad Valenciana–Instituto de Investigación Sanitaria y Biomédica de Alicante Foundation (UGP-14-120, UGP-13-221, UGP-14-265), and the Asociación Española Contra el Cáncer (Fundación Científica GCB13131592CAST). Mar Giner-Calabuig received a pre-doctoral grant from Conselleria d'Educació de la Generalitat Valenciana (VALi+d. EXP ACIF/2010/018, ACIF/2016/002). Miren Alustiza received a pre-doctoral grant from Instituto de Investigación Sanitaria y Biomédica de Alicante ISABIAL. Oscar Murcia received a grant Rio-Hortega from Instituto de Salud Carlos III. Asociación para la Investigación en Gastroenterología de la Provincia de Alicante (AIGPA), a private association that promotes research in gastrointestinal diseases in Alicante, also supported the logistic aspects of the study but declares no conflict of interest.

Publisher Copyright:
© 2020 AGA Institute

Keywords

Colon Tumor
Familial
Genetic
Polyp
Risk

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10.1016/j.cgh.2019.06.012

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Picó, M. D., Castillejo, A., Murcia, Ó., Giner-Calabuig, M., Alustiza, M., Sánchez, A., Moreira, L., Pellise, M., Castells, A., Carrillo-Palau, M., Ramon y Cajal, T., Gisbert-Beamud, A., Llort, G., Yagüe, C., López-Fernández, A., Alvarez-Urturi, C., Cubiella, J., Rivas, L., Rodríguez-Alcalde, D., ... Jover, R. (2020). Clinical and Pathological Characterization of Lynch-Like Syndrome. Clinical Gastroenterology and Hepatology, 18(2), 368-374.e1. https://doi.org/10.1016/j.cgh.2019.06.012

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title = "Clinical and Pathological Characterization of Lynch-Like Syndrome",

abstract = "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.",

keywords = "Colon Tumor, Familial, Genetic, Polyp, Risk",

author = "Pic{\'o}, {Mar{\'i}a Dolores} and Adela Castillejo and {\'O}scar Murcia and Mar Giner-Calabuig and Miren Alustiza and Ariadna S{\'a}nchez and Leticia Moreira and Mar{\'i}a Pellise and Antoni Castells and Marta Carrillo-Palau and {Ramon y Cajal}, Teresa and Alexandra Gisbert-Beamud and Gemma Llort and Carmen Yag{\"u}e and Adri{\'a} L{\'o}pez-Fern{\'a}ndez and Cristina Alvarez-Urturi and Joaquin Cubiella and Laura Rivas and Daniel Rodr{\'i}guez-Alcalde and Maite Herraiz and Catalina Garau and Carlos Dolz and Luis Bujanda and Lucia Cid and Carmen Pov{\'e}s and Marta Garzon and Inmaculada Salces and Marta Ponce and Lu{\'i}s Hern{\'a}ndez-Villalba and Cristina Alenda and Francesc Balaguer and Soto, {Jose Luis} and Rodrigo Jover",

note = "Publisher Copyright: {\textcopyright} 2020 AGA Institute",

year = "2020",

month = feb,

doi = "10.1016/j.cgh.2019.06.012",

language = "Ingl{\'e}s",

volume = "18",

pages = "368--374.e1",

journal = "Clinical Gastroenterology and Hepatology",

issn = "1542-3565",

publisher = "W.B. Saunders Ltd",

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Picó, MD, Castillejo, A, Murcia, Ó, Giner-Calabuig, M, Alustiza, M, Sánchez, A, Moreira, L, Pellise, M, Castells, A, Carrillo-Palau, M, Ramon y Cajal, T, Gisbert-Beamud, A, Llort, G, Yagüe, C, López-Fernández, A, Alvarez-Urturi, C, Cubiella, J, Rivas, L, Rodríguez-Alcalde, D, Herraiz, M, Garau, C, Dolz, C, Bujanda, L, Cid, L, Povés, C, Garzon, M, Salces, I, Ponce, M, Hernández-Villalba, L, Alenda, C, Balaguer, F, Soto, JL & Jover, R 2020, 'Clinical and Pathological Characterization of Lynch-Like Syndrome', Clinical Gastroenterology and Hepatology, vol. 18, no. 2, pp. 368-374.e1. https://doi.org/10.1016/j.cgh.2019.06.012

TY - JOUR

T1 - Clinical and Pathological Characterization of Lynch-Like Syndrome

AU - Picó, María Dolores

AU - Castillejo, Adela

AU - Murcia, Óscar

AU - Giner-Calabuig, Mar

AU - Alustiza, Miren

AU - Sánchez, Ariadna

AU - Moreira, Leticia

AU - Pellise, María

AU - Castells, Antoni

AU - Carrillo-Palau, Marta

AU - Ramon y Cajal, Teresa

AU - Gisbert-Beamud, Alexandra

AU - Llort, Gemma

AU - Yagüe, Carmen

AU - López-Fernández, Adriá

AU - Alvarez-Urturi, Cristina

AU - Cubiella, Joaquin

AU - Rivas, Laura

AU - Rodríguez-Alcalde, Daniel

AU - Herraiz, Maite

AU - Garau, Catalina

AU - Dolz, Carlos

AU - Bujanda, Luis

AU - Cid, Lucia

AU - Povés, Carmen

AU - Garzon, Marta

AU - Salces, Inmaculada

AU - Ponce, Marta

AU - Hernández-Villalba, Luís

AU - Alenda, Cristina

AU - Balaguer, Francesc

AU - Soto, Jose Luis

AU - Jover, Rodrigo

PY - 2020/2

Y1 - 2020/2

N2 - 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.

AB - 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.

KW - Colon Tumor

KW - Familial

KW - Genetic

KW - Polyp

KW - Risk

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U2 - 10.1016/j.cgh.2019.06.012

DO - 10.1016/j.cgh.2019.06.012

M3 - Artículo

C2 - 31220642

AN - SCOPUS:85077643040

SN - 1542-3565

VL - 18

SP - 368-374.e1

JO - Clinical Gastroenterology and Hepatology

JF - Clinical Gastroenterology and Hepatology

IS - 2

ER -

Clinical and Pathological Characterization of Lynch-Like Syndrome

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