Phenotypic heterogeneity of hereditary diffuse gastric cancer: report of a family with early-onset disease

Gullo, Irene; Devezas, Vítor; Baptista, Manuela; Garrido, Luzia; Castedo, Sérgio; Morais, Rui; Wen, Xin; Rios, Elisabete; Pinheiro, Jorge; Pinto-Ribeiro, Inês; Ferreira, Rui M.; Preto, John; Santos-Antunes, João; Marques, Margarida; Campos, Miquel; Almeida, Filipe; Espinheira, Maria do Céu; Dias, Jorge Amil; Figueiredo, Céu; Oliveira, Carla; Trindade, Eunice; Carneiro, Fátima

doi:10.1016/j.gie.2018.02.008

Cited by 43 publications

(27 citation statements)

References 32 publications

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“…First, current guidelines proposed by the IGCLC state that patients with criteria for genetic testing should be assessed from the age of consent, which is generally between 16 and 18 years . At our institution, a 14‐year‐old female was subjected to TG, because of the high risk for GC and the early onset of disease in her family (an 18‐year‐old brother had died with diffuse GC previously) . Endoscopic biopsies were negative.…”

Section: Discussionmentioning

confidence: 99%

“…Two studies on two of these families were published by Oliveira et al . and Gullo et al . Access to clinical data was approved by the Ethics Committee from Centro Hospitalar de São João.…”

Section: Methodsmentioning

confidence: 99%

“…These specimens were from patients from apparently unrelated Portuguese families, with the same pathogenic CDH1 missense variant (c.1901C>T, p.Ala634-Val). Two studies on two of these families were published by Oliveira et al 17 and Gullo et al 18 Access to clinical data was approved by the Ethics Committee from Centro Hospitalar de São João.…”

Section: Methodsmentioning

confidence: 99%

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Pathological features of total gastrectomy specimens from asymptomatic hereditary diffuse gastric cancer patients and implications for clinical management

et al. 2018

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Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant syndrome characterised by multigenerational diffuse gastric cancer, and is mainly caused by germline alterations in the CDH1 gene. Currently, endoscopy has limited diagnostic accuracy, and total gastrectomy (TG) is the treatment of choice for asymptomatic CDH1 carriers. In this study, we aimed to obtain a better understanding of HDGC syndrome by exploring the histopathological findings of TG specimens from asymptomatic HDGC patients. A comprehensive literature review was carried out, searching for TGs performed in asymptomatic HDGC patients. Fourteen unpublished cases, analysed in our institution, were also included. The series encompassed 174 CDH1 carriers. Preoperative endoscopic biopsies were positive in 28.3%. A macroscopic lesion was apparent in 11.7% of TGs. Histopathological analysis revealed intraepithelial lesions and/or intramucosal signet ring cell carcinoma in 87.9% of TGs. When we explored the type of protocol used for handling the specimens, we found that microscopic cancer foci were detected in 95.3% of TGs when a total-embedding protocol (assessment of the totality of gastric mucosa) was applied, and only in 62.5% when no specific protocol was used (P < 0.001). Helicobacter pylori infection was found in 23.4% cases. In conclusion, a thorough histopathological examination of gastric mucosa remains the gold standard for detection of cancer foci in HDGC gastrectomy specimens, requiring experienced pathologists for an accurate diagnosis. A better understanding of the natural history of HDGC will enable better clinical management of HDGC patients, particularly regarding the optimal timing for the performance of TG.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Pathological features of total gastrectomy specimens from asymptomatic hereditary diffuse gastric cancer patients and implications for clinical management

et al. 2018

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“…Humar et al also confirmed that the three-marker haplotype (−160C > A, 48 + 6T > C, 2076C > T) was associated with DGC [35]. In a recent study, impairment of E-cadherin expression was reported with a decreased membranous expression in early lesions of DGC [71]. …”

Section: Factors Associated With Molecular Pathogenicity Of Dgcmentioning

confidence: 91%

“…In 1998, Guilford et al found multiple cases of early-onset DGC in Maori ethnic peoples of New Zealand that were carriers of a three germline truncating mutation in the E-cadherin ( CDH1 ) gene [23]. Several other publications emerged confirming the association of autosomal-dominant pattern of inheritance with germline mutations of the CDH1 gene in the following years [26,71,90,107,140,141,142,143,144,145]. Sporadic DGC has shown germline mutations for CDH1 in a hot spot region between exons 7 and 9, whereas genetic alterations scattered over the entire gene length have been observed for HDGC [146].…”

Section: Hereditary Diffuse Gastric Cancer (Hdgc) and Germline Mutmentioning

confidence: 99%

Diffuse Gastric Cancer: A Summary of Analogous Contributing Factors for Its Molecular Pathogenicity

Ansari

Gantuya

Tuan

et al. 2018

IJMS

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Gastric cancer is the third leading cause of cancer-related deaths and ranks as the fifth most common cancer worldwide. Incidence and mortality differ depending on the geographical region and gastric cancer ranks first in East Asian countries. Although genetic factors, gastric environment, and Helicobacter pylori infection have been associated with the pathogenicity and development of intestinal-type gastric cancer that follows the Correa’s cascade, the pathogenicity of diffuse-type gastric cancer remains mostly unknown and undefined. However, genetic abnormalities in the cell adherence factors, such as E-cadherin and cellular activities that cause impaired cell integrity and physiology, have been documented as contributing factors. In recent years, H. pylori infection has been also associated with the development of diffuse-type gastric cancer. Therefore, in this report, we discuss the host factors as well as the bacterial factors that have been reported as associated factors contributing to the development of diffuse-type gastric cancer.

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Hereditary Diffuse Gastric Cancer Syndrome and the Role of CDH1

2021

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Phenotypic heterogeneity of hereditary diffuse gastric cancer: report of a family with early-onset disease

Cited by 43 publications

References 32 publications

Pathological features of total gastrectomy specimens from asymptomatic hereditary diffuse gastric cancer patients and implications for clinical management

Pathological features of total gastrectomy specimens from asymptomatic hereditary diffuse gastric cancer patients and implications for clinical management

Diffuse Gastric Cancer: A Summary of Analogous Contributing Factors for Its Molecular Pathogenicity

Hereditary Diffuse Gastric Cancer Syndrome and the Role of CDH1

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