Lynch‐like syndrome is as frequent as Lynch syndrome in early‐onset nonfamilial nonpolyposis colorectal cancer

Abstract

Early‐onset (<50 years‐old) nonpolyposis nonfamilial colorectal cancer (EO NP NF CRC) is a common clinical challenge. Although Lynch syndrome (LS) is associated with EO CRC, the frequency of this syndrome in the EO NF cases remains unknown. Besides, mismatch repair deficient (MMRd) CRCs with negative MMR gene testing have recently been described in up to 60% of cases and termed “Lynch‐like syndrome” (LLS). Management and counseling decisions of these patients are complicated because of unconfirmed suspicions of hereditary cancer. To define the prevalence of MMR deficient CRCs, LS and LLS in patients with EO NP NF CRC, we recruited 102 patients with a first diagnosis of NP NF CRC ≤ 50 years old during 2003–2009 who underwent genetic counseling at our institution in Argentina. Tumor immunohistochemical (IHC) MMR for protein expression and microsatellite instability (MSI) status were evaluated, and in those with loss of MLH1 expression by IHC, somatic BRAF V600E mutation and both somatic and germline MLH1 methylation levels were studied. Tumors characterized as MMRd without somatic BRAF mutation nor MLH1 methylation were sent for germline analysis. Twenty one (20.6%) tumors were MMRd. Fourteen of 16 putative LS cases underwent germline testing: 6 pathogenic mutations were identified and 8 cases had no identifiable pathogenic mutations. The prevalence of LS and LLS in this cohort was 5.8% (6/102) and 7.8% (8/102), respectively. As a conclusion we found that 20% of patients with EO NP NF CRC have MMRd tumors, and at least half of these are likely to have LLS.

Comparison of Molecular, Clinicopathological, and Pedigree Differences Between Lynch-like and Lynch Syndromes

“…The difference in the age at onset of CRC between patients with LS and LLS remains controversial; some studies demonstrated similar proportions of early-onset patients in the LS and LLS groups [13], whereas one report showed that the population of patients with LLS was older [30]. Our results supported the latter ndings, with age differences being manifested in both probands and related family members.…”

“…Molecular etiology of LLS still remains unknown, although previous ndings have revealed that some groups of patients with LLS may be a mixture of true LS cases, with non-detected germline variants, and sporadic CRC cases [8,10]. Some researchers found that the risk of CRC was lower in families with LLS than in those with genetically con rmed LS [10,11], while the age of CRC onset was similar for both diseases [12,13]. Nevertheless, the inability to determine the etiology of LLS hampers the development of effective screening and management policies for patients with LLS and the implementation of surveillance recommendations for these individuals and their affected relatives.…”

Clinical and genetic aspects of differential diagnostics of hereditary non-polyposis colorectal cancer

“…Согласно разработанным международным критериям «Амстердам II» СЛ можно предполагать у пациентов с РТК или любым другим /другими ЗНО в составе СЛ (РТМ, рак тонкой кишки, рак мочеточника, рак почки), при наличии не менее 3 родственников со ЗНО из спектра СЛ, а также при соответствии следующим критериям [28] [36]. В среднем на долю ЛПС приходится около 50-60 % всех случаев РТК с MSI-High [37][38][39]. В работе M. Antelo и соавт.…”

“…В работе M. Antelo и соавт. из 14 больных РТК с MSI-High в возрасте до 50 лет СЛ подтвержден только у 43 % пациентов, а в 57 % случаев диагностирован ЛПС [37].…”

Perfil de pacientes com câncer de reto atendidos no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto: estudo transversal

“…Mesmo tendo a genética como fator relacionado, sabe-se que mais de 80% desses tumores são esporádicos e não relacionados a qualquer síndrome genética de alta suscetibilidade. (ANTELO et al, 2019) Estima-se que 30 a 50% dos casos de CCR no mundo se devam a fatores ambientais potencialmente modificáveis como obesidade, dieta, sedentarismo e tabagismo. WILLETT, 2005) Alguns pacientes são assintomáticos, outros podem ter sintomas como mudança do hábito intestinal, incluindo diarreia ou constipação, alteração na coloração das fezes, decorrentes de melena, sangramento retal ou nas fezes, desconforto abdominal inespecífico como cólicas, gases ou dor, sensação de esvaziamento intestinal incompleto, também fraqueza, fadiga, anemia, perda de peso.…”