Hereditary diffuse gastric cancer: laparoscopic surgical approach associated to rare mutattion of CDH1 gene

Campos, Eurico Cleto Ribeiro de; Ribeiro, Saturnino; Higashi, Rafaella; Manfredini, Ricardo; Kfouri, Diogo; Cavalcanti, Teresa Cristina Santos

doi:10.1590/s0102-67202015000200017

Cited by 7 publications

(7 citation statements)

References 9 publications

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“…In the past years, the development of minimally invasive surgery for GC has improved short-term outcomes in total gastrectomy [25,26,27,28,29]. Laparoscopic total gastrectomy in our study and in reports from other groups supports the applicability of this approach and potentially may improve the acceptance of a surgical option by CDH1 mutation carriers [18,30]. The family described in our study with the c.1531C>T variant has a unique profile, in which one of the youngest family members developed an advanced GC and older family members did not.…”

Section: Discussionsupporting

confidence: 74%

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Identification of c.1531C>T Pathogenic Variant in the CDH1 Gene as a Novel Germline Mutation of Hereditary Diffuse Gastric Cancer

Norero

Alarcon

Hakkaart

et al. 2019

IJMS

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Germline pathogenic variants in the CDH1 gene are a well-established cause of hereditary diffuse gastric cancer (HDGC) syndrome. The aim of this study was to characterize CDH1 mutations associated with HDGC from Chile, a country with one of the highest incidence and mortality rates in the world for gastric cancer (GC). Here, we prospectively include probands with family history/early onset of diffuse-type of GC. The whole coding sequence of the CDH1 gene was sequenced from genomic DNA in all patients, and a multidisciplinary team managed each family member with a pathogenic sequence variant. Thirty-six cases were included (median age 44 years/male 50%). Twenty-seven (75%) patients had diffuse-type GC at ≤50 years of age and 19 (53%) had first or second-degree family members with a history of HDGC. Two cases (5.5%) carried a non-synonymous germline sequence variant in the CDH1 gene: (a) The c.88C>A missense variant was found in a family with three diffuse-type GC cases; and (b) c.1531C>T a nonsense pathogenic variant was identified in a 22-year-old proband with no previous family history of HDGC. Of note, six family members carry the same nonsense pathogenic variant. Prophylactic gastrectomy in the proband’s sister revealed stage I signet-ring cell carcinoma. The finding of 1531C>T pathogenic variant in the CDH1 in proband with no previous family history of HDGC warrants further study to uncover familial clustering of disease in CDH1 negative patients. This finding may be particularly relevant in high incidence countries, such as the case in this report.

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Section: Discussionsupporting

confidence: 74%

“…In Latin America, only Colombia and Brazil have reported CDH1 mutations associated with HDGC [17,18,19]. In Chile, with the highest incidence and mortality rates of GC in the region, family clustering in terms of hereditary disease of GC has not been directly addressed.…”

Section: Introductionmentioning

confidence: 99%

Identification of c.1531C>T Pathogenic Variant in the CDH1 Gene as a Novel Germline Mutation of Hereditary Diffuse Gastric Cancer

Norero

Alarcon

Hakkaart

et al. 2019

IJMS

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“…4 Several reports showed that, in almost 100% of the TGs performed in asymptomatic CDH1 carriers, cancer foci (pT1a) were identified. 12,16,[24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] Intramucosal cancer foci are usually tiny, ranging between <0.1 mm and 10 mm in E,F, Reactive lymphoid follicle in the gastric body of a CDH1 carrier subjected to total gastrectomy (E), in close proximity to (arrowhead) (F) a cluster of pseudo-SRCs. 62 diameter, 42,43 and, in some cases, only a single focus was identified.…”

Section: Discussionmentioning

confidence: 99%

“…TG remains the best clinical management option for HDGC patients with a proven germline, pathogenic CDH1 variant . Several reports showed that, in almost 100% of the TGs performed in asymptomatic CDH1 carriers, cancer foci (pT1a) were identified . Intramucosal cancer foci are usually tiny, ranging between <0.1 mm and 10 mm in diameter, and, in some cases, only a single focus was identified …”

Section: Discussionmentioning

confidence: 99%

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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“…All the 42 patients were found to have signet ring cell adenocarcinoma on tissue morphology. Some of the mutations studied in the patients were found to have either missense mutation or frameshift mutation, missense mutation being the commonest [18][19][20][21][22][23][24][25][26][27]. A study was conducted by Brooks-Wilson et al, which included 43 different families, 42 positive for DGC and the other one being intestinal type and in the study, CDH1 mutations were found in more than 30% of the families and 12 of those families showed familial history of multiple cases of gastric and lobular breast cancer with an autosomal dominant inheritance pattern of these mutations and almost 50% of those mutations were found to have a germline truncating CDH1 mutations [28].…”

Section: A Hereditary Diffuse Gastric Cancermentioning

confidence: 99%

Significance of E-cadherin Gene Mutations in Patients With Hereditary Diffuse Gastric Cancer Syndrome: A Systematic Review

Goud

Mehkari

Mohammed

et al. 2020

Cureus

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Gastric cancer is the third-most fatal cancer in the world. Though over the years, we saw patients mostly with intestinal type accounting for the highest mortality rate, the recent rise of the diffuse form with germline E-cadherin (CDH1) mutations has added a whole new level of interest to study in detail about the association between CDH1 and diffuse gastric cancer (DGC). This introduced a set guideline formulated by Internal Gastric Cancer Linkage Consortium (IGCLC) for patients with family history of diffuse gastric cancer and invasive lobular breast cancer (ILBC). The analysis of this link was also important to set proper management protocol for patients who were CDH1 mutation carriers which now involves genetic counselling, endoscopic surveillance and screening and prophylactic total gastrectomy (PTG). The study was conducted in accordance to the 'PRISMA guidelines for reporting systematic review and meta-analysis'. Peer-reviewed studies were included from the PubMed database and relevant articles were selected to be included in the study. Appropriate inclusion/exclusion criteria with free full text English articles were applied while selecting the articles. A total of 10 studies on review with different study populations showed that of the 42 patients who were diagnosed with diffuse gastric cancer, 88% of them showed a positive germline E-cadherin gene mutation and 100% of the CDH1 mutation carriers showed microscopic changes of signet ring cell adenocarcinoma of the stomach. The beneficial effects of PTG with better survival rates and low mortality rates has outweighed other treatment modalities. Laparoscopic approach has proved to be more useful and a safer approach for gastrectomy surgeries with better post-operative management. The need for prophylactic mastectomy is also increased in the recent times and thus this requires a new set of guidelines for ILBC patients with hereditary diffuse gastric cancer (HDGC) syndrome.

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Hereditary diffuse gastric cancer: laparoscopic surgical approach associated to rare mutattion of CDH1 gene

Cited by 7 publications

References 9 publications

Identification of c.1531C>T Pathogenic Variant in the CDH1 Gene as a Novel Germline Mutation of Hereditary Diffuse Gastric Cancer

Identification of c.1531C>T Pathogenic Variant in the CDH1 Gene as a Novel Germline Mutation of Hereditary Diffuse Gastric Cancer

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

Significance of E-cadherin Gene Mutations in Patients With Hereditary Diffuse Gastric Cancer Syndrome: A Systematic Review

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