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Article: Clinicopathological and Molecular Insights into Gallbladder Cancer.

de Reuver, Philip R / van der Post, Rachel S

2023 Volume 15, Issue 10

Abstract: Although gallbladder cancer (GBC) is rare, it is one of the few cancers with a higher mortality rate than incidence, accounting for 1 [ ... ]. ...

Abstract	Although gallbladder cancer (GBC) is rare, it is one of the few cancers with a higher mortality rate than incidence, accounting for 1 [...].
Language	English
Publishing date	2023-05-12
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15102728
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Article: The influence of

Zhou, Chengliang / Bisseling, Tanya M / van der Post, Rachel S / Boleij, Annemarie

Computational and structural biotechnology journal

2023 Volume 23, Page(s) 186–198

Abstract: Helicobacter ... ...

Abstract	Helicobacter pylori
Language	English
Publishing date	2023-11-30
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2694435-2
ISSN	2001-0370
ISSN	2001-0370
DOI	10.1016/j.csbj.2023.11.053
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Article ; Online: Shifting perceptions on endoscopic surveillance and timing of prophylactic gastrectomy for hereditary diffuse gastric cancer.

van Dieren, Jolanda M / van der Post, Rachel S / Bisseling, Tanya M

The British journal of surgery

2023 Volume 110, Issue 9, Page(s) 1028–1029

MeSH term(s)	Humans ; Stomach Neoplasms/genetics ; Stomach Neoplasms/prevention & control ; Stomach Neoplasms/surgery ; Gastrectomy ; Mutation ; Adenocarcinoma/surgery ; Cadherins/genetics ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Neoplastic Syndromes, Hereditary/surgery
Chemical Substances	Cadherins
Language	English
Publishing date	2023-06-18
Publishing country	England
Document type	Journal Article
ZDB-ID	2985-3
ISSN	1365-2168 ; 0263-1202 ; 0007-1323 ; 1355-7688
ISSN (online)	1365-2168
ISSN	0263-1202 ; 0007-1323 ; 1355-7688
DOI	10.1093/bjs/znad192
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Article ; Online: Diffuse gastric cancer: Emerging mechanisms of tumor initiation and progression.

Monster, Jooske L / Kemp, Lars J S / Gloerich, Martijn / van der Post, Rachel S

Biochimica et biophysica acta. Reviews on cancer

2022 Volume 1877, Issue 3, Page(s) 188719

Abstract: Gastric cancer is globally the fourth leading cause of cancer-related deaths. Patients with diffuse-type gastric cancer (DGC) particularly have a poor prognosis that only marginally improved over the last decades, as conventional chemotherapies are ... ...

Abstract	Gastric cancer is globally the fourth leading cause of cancer-related deaths. Patients with diffuse-type gastric cancer (DGC) particularly have a poor prognosis that only marginally improved over the last decades, as conventional chemotherapies are frequently ineffective and specific therapies are unavailable. Early-stage DGC is characterized by intramucosal lesions of discohesive cells, which can be present for many years before the emergence of advanced DGC consisting of highly proliferative and invasive cells. The mechanisms underlying the key steps of DGC development and transition to aggressive tumors are starting to emerge. Novel mouse and organoid models for DGC, together with multi-omic analyses of DGC tumors, revealed contributions of both tumor cell-intrinsic alterations and gradual changes in the tumor microenvironment to DGC progression. In this review, we will discuss how these recent findings are leading towards an understanding of the cellular and molecular mechanisms responsible for DGC initiation and malignancy, which may provide opportunities for targeted therapies.
MeSH term(s)	Animals ; Cell Transformation, Neoplastic ; Humans ; Mice ; Stomach Neoplasms/pathology ; Tumor Microenvironment
Language	English
Publishing date	2022-03-17
Publishing country	Netherlands
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2918802-7
ISSN	1879-2561 ; 0304-419X
ISSN (online)	1879-2561
ISSN	0304-419X
DOI	10.1016/j.bbcan.2022.188719
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Article ; Online: Referral rate of patients with incidental gallbladder cancer and survival: outcomes of a multicentre retrospective study.

van Dooren, Mike / de Savornin Lohman, Elise A J / van der Post, Rachel S / Erdmann, Joris I / Hoogwater, Frederik J H / Groot Koerkamp, Bas / van den Boezem, Peter B / de Reuver, Philip R

BJS open

2024 Volume 8, Issue 2

Abstract: Background: Treatment outcomes of incidental gallbladder cancer generally stem from tertiary referral centres, while many patients are initially diagnosed and managed in secondary care centres. Referral patterns of patients with incidental gallbladder ... ...

Abstract	Background: Treatment outcomes of incidental gallbladder cancer generally stem from tertiary referral centres, while many patients are initially diagnosed and managed in secondary care centres. Referral patterns of patients with incidental gallbladder cancer are poorly reported. This study aimed to evaluate incidental gallbladder cancer treatment in secondary centres, rates of referral to tertiary centres and its impact on survival. Methods: Medical records of patients with incidental gallbladder cancer diagnosed between 2000 and 2019 in 27 Dutch secondary centres were retrospectively reviewed. Patient characteristics, surgical treatment, tumour characteristics, referral pattern and survival were assessed. Predictors for overall survival were determined using multivariable Cox regression. Results: In total, 382 patients with incidental gallbladder cancer were included. Of 243 patients eligible for re-resection (pT1b-pT3, M0), 131 (53.9%) were referred to a tertiary centre. The reason not to refer, despite indication for re-resection, was not documented for 52 of 112 non-referred patients (46.4%). In total, 98 patients underwent additional surgery with curative intent (40.3%), 12 of these in the secondary centre. Median overall survival was 33 months (95% c.i. 24 to 42 months) in referred patients versus 17 months (95% c.i. 3 to 31 months) in the non-referred group (P = 0.019). Referral to a tertiary centre was independently associated with improved survival after correction for age, ASA classification, tumour stage and resection margin (HR 0.60, 95% c.i. 0.38 to 0.97; P = 0.037). Conclusion: Poor incidental gallbladder cancer referral rates were associated with worse survival. Age, performance status, resection margin or tumour stage should not preclude referral of a patient with incidental gallbladder cancer to a tertiary centre.
MeSH term(s)	Humans ; Gallbladder Neoplasms/epidemiology ; Gallbladder Neoplasms/surgery ; Gallbladder Neoplasms/diagnosis ; Retrospective Studies ; Margins of Excision ; Incidental Findings ; Neoplasm Staging ; Referral and Consultation
Language	English
Publishing date	2024-03-22
Publishing country	England
Document type	Multicenter Study ; Journal Article
ISSN	2474-9842
ISSN (online)	2474-9842
DOI	10.1093/bjsopen/zrae013
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Article ; Online: Cell division-dependent dissemination following E-cadherin loss underlies initiation of diffuse-type gastric cancer.

Monster, Jooske L / Kemp, Lars Js / Busslinger, Georg A / Vliem, Marjolein J / Derks, Lucca Lm / Staes, Annelot Al / Bisseling, Tanya M / Clevers, Hans / van der Post, Rachel S / Gloerich, Martijn

The Journal of pathology

2024 Volume 263, Issue 2, Page(s) 226–241

Abstract: Loss of the cell-cell adhesion protein E-cadherin underlies the development of diffuse-type gastric cancer (DGC), which is characterized by the gradual accumulation of tumor cells originating from the gastric epithelium in the surrounding stroma. How E- ... ...

Abstract	Loss of the cell-cell adhesion protein E-cadherin underlies the development of diffuse-type gastric cancer (DGC), which is characterized by the gradual accumulation of tumor cells originating from the gastric epithelium in the surrounding stroma. How E-cadherin deficiency drives DGC formation remains elusive. Therefore, we investigated the consequences of E-cadherin loss on gastric epithelial organization utilizing a human gastric organoid model and histological analyses of early-stage DGC lesions. E-cadherin depletion from gastric organoids recapitulates DGC initiation, with progressive loss of a single-layered architecture and detachment of individual cells. We found that E-cadherin deficiency in gastric epithelia does not lead to a general loss of epithelial cohesion but disrupts the spindle orientation machinery. This leads to a loss of planar cell division orientation and, consequently, daughter cells are positioned outside of the gastric epithelial layer. Although basally delaminated cells fail to detach and instead reintegrate into the epithelium, apically mispositioned daughter cells can trigger the gradual loss of the single-layered epithelial architecture. This impaired architecture hampers reintegration of mispositioned daughter cells and enables basally delaminated cells to disseminate into the surrounding matrix. Taken together, our findings describe how E-cadherin deficiency disrupts gastric epithelial architecture through displacement of dividing cells and provide new insights in the onset of DGC. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
MeSH term(s)	Stomach Neoplasms/pathology ; Stomach Neoplasms/metabolism ; Cadherins/metabolism ; Humans ; Organoids/pathology ; Organoids/metabolism ; Cell Division ; Gastric Mucosa/pathology ; Gastric Mucosa/metabolism ; Cell Movement ; Antigens, CD/metabolism ; Epithelial Cells/pathology ; Epithelial Cells/metabolism
Chemical Substances	Cadherins ; CDH1 protein, human ; Antigens, CD
Language	English
Publishing date	2024-04-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3119-7
ISSN	1096-9896 ; 0022-3417
ISSN (online)	1096-9896
ISSN	0022-3417
DOI	10.1002/path.6277
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Article ; Online: Biological background of colorectal polyps and carcinomas with heterotopic ossification: A national study and literature review.

Vos, Anne-Marie / Pijnenborg, Lieke / van Vliet, Shannon / Kodach, Liudmila L / Ciompi, Francesco / van der Post, Rachel S / Simmer, Femke / Nagtegaal, Iris D

Human pathology

2024 Volume 145, Page(s) 34–41

Abstract: The biological mechanisms and potential clinical impact of heterotopic ossification (HO) in colorectal neoplasms are not fully understood. This study investigates the clinicopathological characteristics of colorectal neoplasms associated with HO and ... ...

Abstract	The biological mechanisms and potential clinical impact of heterotopic ossification (HO) in colorectal neoplasms are not fully understood. This study investigates the clinicopathological characteristics of colorectal neoplasms associated with HO and examines the potential role of the bone morphogenetic protein (BMP) pathway in development of HO. An artificial intelligence (AI) based classification of colorectal cancers (CRC) exhibiting HO and their association with consensus molecular subtypes (CMS) is performed. The study included 77 cases via the Dutch nationwide Pathology databank. Immunohistochemistry for BMP2, SMAD4, and Osterix was performed. An AI algorithm assessed the tumour-stroma ratio to approximate the CMS. A literature search yielded 96 case reports, which were analysed and compared with our cases for clinicopathological parameters. HO was more frequently observed in our cohort in traditional serrated adenomas (25%), tubulovillous adenomas (25%) and juvenile polyps (25%), while in the literature it was most often seen in juvenile polyps (38.2%) and inflammatory polyps (29.4%). In both cohorts, carcinomas were mostly conventional (>60%) followed by mucinous and serrated adenocarcinomas. Higher expression of BMP2, SMAD4, and Osterix was observed in tumour and/or stromal cells directly surrounding bone, indicating activation of the BMP pathway. The tumour-stroma analysis appointed >50% of the cases to the mesenchymal subtype (CMS4) (59%). HO has a predilection for serrated and juvenile/inflammatory polyps, mucinous and serrated adenocarcinomas. BMP signalling is activated and seems to play a role in formation of HO in colorectal neoplasms. In line with TGFβ/BMP pathway activation associated with CMS4 CRC, HO seems associated with CMS4.
MeSH term(s)	Humans ; Colonic Polyps/pathology ; Artificial Intelligence ; Adenoma/pathology ; Colorectal Neoplasms/pathology ; Intestinal Polyps ; Carcinoma ; Adenocarcinoma ; Ossification, Heterotopic
Language	English
Publishing date	2024-02-15
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	207657-3
ISSN	1532-8392 ; 0046-8177
ISSN (online)	1532-8392
ISSN	0046-8177
DOI	10.1016/j.humpath.2024.02.006
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Article ; Online: Deficient mismatch repair screening of advanced adenomas in the population screening program for colorectal cancer is not effective.

Vink-Börger, Elisa / Dabir, Parag D / Krekels, Joyce / van Kouwen, Mariëtte C A / Ligtenberg, Marjolijn J L / van der Post, Rachel S / Nagtegaal, Iris D

Histopathology

2024 Volume 84, Issue 6, Page(s) 1056–1060

Abstract: Aim: Currently, screening of colorectal cancers (CRC) by assessing mismatch repair deficiency (dMMR) or microsatellite instability (MSI) is used to identify Lynch syndrome (LS) patients. Advanced adenomas are considered immediate precursor lesions of ... ...

Abstract	Aim: Currently, screening of colorectal cancers (CRC) by assessing mismatch repair deficiency (dMMR) or microsatellite instability (MSI) is used to identify Lynch syndrome (LS) patients. Advanced adenomas are considered immediate precursor lesions of CRC. In this study we investigate the relevance of screening of advanced adenomas for LS in population screening. Methods and results: Advanced adenomas (n = 1572) were selected from the Dutch colorectal cancer population screening programme, based on one or more of the criteria: tubulovillous (n = 848, 54%) or villous adenoma (n = 118, 7.5%), diameter ≥ 1 cm (n = 1286, 82%) and/or high-grade dysplasia (n = 176, 11%). In 86 cases (5%), all three criteria were fulfilled at the same time. MMR-IHC and/or MSI analyses were performed on all cases. Only five advanced adenomas (0.3%) showed dMMR and MSI, including two cases with hypermethylation. In at least two patients a germline event was suspected based on allelic frequencies. No pathogenic explanation was found in the last case. Conclusion: Timely testing of precursor lesions would be preferable to detect new LS patients before CRC development. However, standard assessment of dMMR of advanced adenomas from the population screening is not effective.
MeSH term(s)	Humans ; DNA Mismatch Repair/genetics ; Early Detection of Cancer ; Colorectal Neoplasms/diagnosis ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis ; Colorectal Neoplasms, Hereditary Nonpolyposis/genetics ; Colorectal Neoplasms, Hereditary Nonpolyposis/pathology ; Adenoma/diagnosis ; Adenoma/genetics ; Microsatellite Instability ; Brain Neoplasms ; Neoplastic Syndromes, Hereditary
Language	English
Publishing date	2024-01-26
Publishing country	England
Document type	Journal Article
ZDB-ID	131914-0
ISSN	1365-2559 ; 0309-0167
ISSN (online)	1365-2559
ISSN	0309-0167
DOI	10.1111/his.15150
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Article ; Online: Gastric Epithelial Polyps: When to Ponder, When to Panic.

Vos, Shoko / van der Post, Rachel S / Brosens, Lodewijk A A

Surgical pathology clinics

2020 Volume 13, Issue 3, Page(s) 431–452

Abstract: This review provides an overview of different types of gastric epithelial polyps. The polyps are classified based on their cell or epithelial compartment of origin. Some of these polyps can be considered reactive or nonneoplastic, whereas others are ... ...

Abstract	This review provides an overview of different types of gastric epithelial polyps. The polyps are classified based on their cell or epithelial compartment of origin. Some of these polyps can be considered reactive or nonneoplastic, whereas others are neoplastic in origin, are sometimes associated with a hereditary polyposis/cancer syndrome, and may have malignant potential. The aim of this review is to provide a pragmatic overview for the practicing pathologist about how to correctly diagnose and deal with gastric epithelial polyps and when (not) to ponder, and when (not) to panic.
MeSH term(s)	Adenomatous Polyps/diagnosis ; Adenomatous Polyps/pathology ; Biopsy ; Diagnosis, Differential ; Gastric Fundus/pathology ; Humans ; Prognosis ; Stomach/pathology ; Stomach Neoplasms/diagnosis ; Stomach Neoplasms/pathology
Language	English
Publishing date	2020-07-11
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1875-9157
ISSN (online)	1875-9157
DOI	10.1016/j.path.2020.05.004
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Article ; Online: Recent advances in the pathology of heritable gastric cancer syndromes.

Gullo, Irene / van der Post, Rachel S / Carneiro, Fátima

Histopathology

2020 Volume 78, Issue 1, Page(s) 125–147

Abstract: Despite the relative rarity of hereditary gastric cancer syndromes, the prompt recognition of their specific clinical features and histopathological characteristics is pivotal in offering patients the most appropriate treatment. In this article, we ... ...

Abstract	Despite the relative rarity of hereditary gastric cancer syndromes, the prompt recognition of their specific clinical features and histopathological characteristics is pivotal in offering patients the most appropriate treatment. In this article, we address the three major inherited syndromes that primarily affect the stomach: hereditary diffuse gastric cancer (HDGC), caused by germline variants in CDH1 and CTNNA1; gastric adenocarcinoma and proximal polyposis of the stomach, caused by germline mutations in promoter 1B of APC; and familial intestinal gastric cancer, which has a poorly defined genetic cause. The main focus will be on HDGC, in light of the recent publication of updated clinical practice guidelines and emerging concepts regarding HDGC histopathology. In particular, we describe the broad morphological spectrum of HDGC lesions, stressing the importance of recognising indolent and aggressive phenotypes. Moreover, we discuss the increased risk of gastric (pre)malignancies developing in patients with other well-defined hereditary cancer syndromes, such as familial adenomatous polyposis, Lynch syndrome, Peutz-Jeghers syndrome, juvenile polyposis, Li-Fraumeni syndrome, and hereditary breast and ovarian cancer syndrome.
MeSH term(s)	Adenocarcinoma/genetics ; Adenocarcinoma/pathology ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Humans ; Neoplastic Syndromes, Hereditary/genetics ; Neoplastic Syndromes, Hereditary/pathology ; Stomach/pathology ; Stomach Neoplasms/genetics ; Stomach Neoplasms/pathology
Language	English
Publishing date	2020-12-31
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	131914-0
ISSN	1365-2559 ; 0309-0167
ISSN (online)	1365-2559
ISSN	0309-0167
DOI	10.1111/his.14228
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