Hereditary diffuse gastric cancer – An overview

Gurzu, Simona; Jung, Ioan; Orłowska, Janina; Sugimura, Haruhiko; Kádár, Zoltán; Turdean, Sabin Gligore; Bara, Tivadar

doi:10.1016/j.prp.2015.06.003

Cited by 11 publications

(9 citation statements)

References 31 publications

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“…The multicentric poorly cohesive carcinoma with intraepithelial pagetoid onset was mostly considered to be the characteristic for hereditary diffuse gastric cancer (HDGC) at the early onset 15 – 17 or for CDH1 germ-line mutation carriers. 18 However, these CDH1 -mutant tumors usually display signet-ring cell architecture and are E-cadherin negative.…”

Section: Discussionmentioning

confidence: 99%

New Insights in Histogenetic Pathways of Gastric Cancer

et al. 2015

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The aim of this paper was to describe 3 possible histogenetic pathways for poorly cohesive (diffuse) carcinomas and 2 for intestinal-type gastric carcinomas (GCs), which might influence the behavior of GC. In the present observational study, 102 patients with early (n = 50) and advanced GCs (n = 52) were evaluated, and the histogenetic background was analyzed. All of the cases were sporadic GCs. For particular aspects, Maspin, E-cadherin, and SLUG immunostains were performed. For our final conclusions, the results were correlated with literature data. In early stages, poorly cohesive carcinomas can display 3 histogenetic pathways, with particular molecular behaviors: “carcinoma with intraepithelial pagetoid onset” (with or without a switch from E-cadherin to SLUG positivity), “carcinoma with early lymphatic invasion” (carcinoma limited to mucosa but with carcinomatosis of the lymph vessels from subjacent layers), and “microglandular-type poorly cohesive carcinoma” (the onset is similar with adenocarcinoma but abrupt dedifferentiation can be seen in the submucosa, with persistence of a dual component in the deep layers). The intestinal type carcinoma can be developed on the background of superficially located dysplasia (“classic adenocarcinoma”) or in the submucosal heterotopic mucosa (“adenocarcinoma arising from the mucosal infolding in the submucosa”). Based on personal observations correlated with literature data, 5 histopathogenetic pathways are proposed with specific denominations. Each of them can partially explain the aberrant behavior of early gastric cancer.

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Section: Discussionmentioning

confidence: 99%

New Insights in Histogenetic Pathways of Gastric Cancer

et al. 2015

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“…Another parameter that should be attentively examined in patients with EGC is the tumor multifocality or multicentricity. This characteristic was especially observed in hereditary diffuse gastric cancers [ 22 ], but acquired diffuse cancers can also have a multicentric aspect, being known as “carcinomas with intraepithelial pagetoid onset” [ 19 ]. Because the intramucosal foci are difficult to detect endoscopically [ 19 , 22 ], description of multifocality in the histopathological report is a valuable parameter for endoscopic follow-up of patients who have undergone endoscopic resection or subtotal gastrectomy.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical features and staging of early gastric cancer

Gurzu

Orłowska

Sugimura

et al. 2017

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IntroductionThe aim of this study was to analyze the particularities of early gastric cancer (EGC) and their importance for staging, prognosis, and therapy.Material and methodsA total of 338 GCs diagnosed and surgically removed in three medical institutes from Eastern Europe were retrospectively examined, and the EGCs were further examined. Besides the demographic factors and tumor characteristics, immunostains were performed with E-cadherin, HER-2, p53, Ki67, MLH-1, MSH-2, COX-2, VEGF-A, CD31, and CD105.ResultsFrom the 338 GCs, 29 were EGCs, the average being similar in Poland and Hungary (12.37% and 13.33% respectively) but lower in Romania (5.61%). The rate of lymph node metastases was 20.69% (n = 6). Two of the cases presented liver metastases, both of them having a multifocal aspect. In 1 of these cases, limited to the mucosa, intramural carcinomatosis of the lymph vessels was seen in submucosa, muscularis propria, and subserosa. COX-2 positivity was observed in 14 (48.72%) cases. COX-2 was directly correlated with microvessel density determined with CD31 (p < 0.001) and CD105 (p = 0.03). Same correlation with CD31 and CD105 was seen for HER-2 (p = 0.03 and p = 0.0007). The only negative independent prognostic factors for overall survival were tumor localization at the proximal stomach and male gender, regardless of age.ConclusionsIn EGCs, intramural carcinomatosis of the lymph vessels and multifocality should be separately described in every surgical pathology report, as indicators of aggressiveness. Microsatellite status, E-cadherin, HER-2, p53, and Ki67 do not have prognostic value in EGC, but the highly angiogenic pattern is a possible therapeutic target.

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“…The syndrome of HDGC is responsible for 3% of gastric cancers (4,10), and lobular breast carcinoma is the second-most common neoplasm in HDGC families (12). Inherited causative mutations in the E-cadherin gene (CDH1) located at 16q22.1 initiate the majority of HDGC´s (11,13).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…The PCR/Sequencing primers and the amplification conditions are listed in Table 1. All Sanger sequencing experiments were performed by BigDye Terminator v.3.1 chemistry (Life Technologies, Foster City, NJ) on ABI PRISM 3100 DNA sequencer (Life Technologies) using a standard protocol.Discussion:Familial clustering is observed in 10% of patients who have gastric carcinoma(4,10). Until now, 3 familial gastric cancer syndromes have been identified: hereditary diffuse gastric cancer (HDGC), familial intestinal gastric cancer (FIGC) and gastric adenocarcinoma with proximal polyposis of the stomach (GAPPS)(5,11).…”

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confidence: 99%