Search Results (23)

Tumor budding is increasingly recognized as a histopathologic feature associated with invasive behavior in gastrointestinal malignancies. While its prognostic value is well established in colorectal carcinoma, its significance in gastric adenocarcinoma remains less clearly defined because of marked morphologic heterogeneity, variable growth patterns, and the absence of gastric-specific assessment criteria. Multiple studies have associated high budding density with adverse clinicopathologic features, including lymph node metastasis, lymphovascular invasion, advanced tumor stage, and poorer survival, particularly in intestinal-type tumors. However, these associations are more difficult to interpret in diffuse-type and mixed carcinomas, where intrinsic discohesion and architectural variability complicate the distinction between true budding and baseline growth patterns. Beyond prognostic assessment, tumor budding has been linked to localized alterations in cell adhesion, cytoskeletal organization, tumor–stroma interaction, and partial epithelial–mesenchymal transition. Emerging evidence also suggests that its biological significance may differ across molecular subtypes of gastric cancer. This review examines the current evidence on the definition, morphologic spectrum, methodological limitations, and biologic context of tumor budding in gastric adenocarcinoma. We propose that, in gastric cancer, tumor budding is best interpreted not as a uniformly applicable scoring parameter, but as a context-dependent morphologic indicator of invasive tumor remodeling whose meaning varies according to tumor architecture, stromal interface, and molecular subtype. Full article

Objective: To identify distinctive 18F-FDG positron emission tomography (PET)/computer tomography (CT) features of gastric-type endocervical adenocarcinoma (GAS) that differentiate it from squamous cell carcinoma (SCC) and usual-type endocervical adenocarcinoma (UEA), as well as to correlate these findings with pathological characteristics. Methods: Patients treated between December 2018 and December 2024 were retrospectively reviewed. The study included 12 GAS, 48 SCC, and 30 UEA cases. Evaluated parameters included tumor morphology, cystic components, uterine cavity fluid, N/M staging, tumor diameter, the cervical lesion maximum standardized uptake value (SUVmax), and the tumor-to-liver maximum standardized uptake ratio (T/L SUVmax). Results: GAS predominantly exhibited diffuse infiltrative growth (11/12), in contrast to mass-like growth observed in SCC (37/48) and UEA (24/30) (both p < 0.001). Cystic components, uterine cavity fluid, and peritoneal metastasis occurred significantly more frequently in GAS (12/12, 11/12, 5/12, respectively) compared to SCC and UEA (all p < 0.001). Elevated CA19-9 levels were more common in GAS (9/12) compared with SCC (p < 0.001). Tumor diameter did not differ significantly among the groups (p > 0.05). SUVmax and T/L SUVmax values were significantly lower in GAS (7.5 ± 3.8 and 2.5 ± 1.6, respectively) than in UEA (19.1 ± 11.4 and 5.7 ± 3.4) and SCC (17.4 ± 6.7 and 5.5 ± 2.6) (all p < 0.001). Conclusion: The clinical characteristics of GAS include infiltrative tumor growth, fluid accumulation in the uterine cavity, frequent formation of microcystic or macrocystic components, peritoneal metastasis, and elevated CA19-9 levels. In this cohort, SUVmax and T/L SUVmax values in GAS were significantly lower than those observed in SCC and UEA. Full article

Gastric cancer is the fifth most common cancer and the fourth cause of global cancer mortality. The identification of new biomarkers and drug targets is crucial to allow the better prognosis and treatment of patients. The mitotic spindle positioning (MISP) protein has the function of correcting mitotic spindle positioning and centrosome clustering and has been implicated in the cytokinesis and migration of cancer cells. The goal of this work was to evaluate the expression and clinical relevance of MISP in gastric cancer. MISP expression was evaluated by immunohistochemistry in a single hospital series (n = 286) of gastric adenocarcinomas and compared with normal gastric mucosa and intestinal metaplasia, a preneoplastic lesion. MISP was detected on the membrane in 83% of the cases, being overexpressed in gastric cancer compared to normal gastric mucosa (n = 10). Its expression was negatively associated with diffuse and poorly cohesive types. On the other hand, it was strongly expressed in intestinal metaplasia where it was associated with MUC2 and CDX2 expression. Furthermore, when we silenced MISP in vitro, a significant decrease in the viability of gastric carcinoma cells was observed. In conclusion, MISP is overexpressed in gastric cancer, being associated with an intestinal phenotype in gastric carcinogenesis and having a role in cellular proliferation. Full article

The most well-characterized hereditary form of gastric cancer is hereditary diffuse gastric cancer (HDGC), an autosomal dominant syndrome characterized by an increased risk of diffuse gastric and lobular breast cancer. HDGC is predominantly caused by germline pathogenic variants in the CDH1 gene, and more rarely in the CTNNA1 gene. Furthermore, the International Gastric Cancer Linkage Consortium (IGCLC) guidelines do not clarify whether or not mixed gastric cancer (with a diffuse component) should be considered in the HDGC genetic testing criteria. We aimed to evaluate the contribution of CTNNA1 and CTNND1 germline variants to HDGC. Additionally, we also intended to compare the frequencies of CDH1 and CTNNA1 (and eventually CTNND1) germline variants between patients with diffuse and mixed gastric carcinomas to evaluate if genetic testing for these genes should or should not be considered in patients with the latter. We analyzed the CDH1 gene in 67 cases affected with early-onset/familial mixed gastric carcinomas and the CTNNA1 and CTNND1 genes in 208 cases with diffuse or mixed gastric cancer who had tested negative for CDH1 pathogenic germline variants. A deleterious CTNNA1 germline variant was found in 0.7% (1/141) of diffuse gastric cancer patients meeting the 2020 IGCLC criteria, as compared to the rate of 2.8% of CDH1 deleterious variants found by us in this setting. No deleterious variants were found in CTNND1, but six variants of uncertain significance were identified in this gene. We did not find any pathogenic CDH1, CTNNA1 or CTNND1 variant in index patients with early-onset/familial mixed gastric cancer, so there is no evidence that supports including this tumor type in the testing criteria for germline variants in these genes. The role of the CTNND1 gene in inherited gastric cancer predisposition is still unclear. Full article

Aim: To improve identification of peritoneal and distant metastases in locally advanced gastric cancer using [¹⁸F]FDG-PET radiomics. Methods: [¹⁸F]FDG-PET scans of 206 patients acquired in 16 different Dutch hospitals in the prospective multicentre PLASTIC-study were analysed. Tumours were delineated and 105 radiomic features were extracted. Three classification models were developed to identify peritoneal and distant metastases (incidence: 21%): a model with clinical variables, a model with radiomic features, and a clinicoradiomic model, combining clinical variables and radiomic features. A least absolute shrinkage and selection operator (LASSO) regression classifier was trained and evaluated in a 100-times repeated random split, stratified for the presence of peritoneal and distant metastases. To exclude features with high mutual correlations, redundancy filtering of the Pearson correlation matrix was performed (r = 0.9). Model performances were expressed by the area under the receiver operating characteristic curve (AUC). In addition, subgroup analyses based on Lauren classification were performed. Results: None of the models could identify metastases with low AUCs of 0.59, 0.51, and 0.56, for the clinical, radiomic, and clinicoradiomic model, respectively. Subgroup analysis of intestinal and mixed-type tumours resulted in low AUCs of 0.67 and 0.60 for the clinical and radiomic models, and a moderate AUC of 0.71 in the clinicoradiomic model. Subgroup analysis of diffuse-type tumours did not improve the classification performance. Conclusion: Overall, [¹⁸F]FDG-PET-based radiomics did not contribute to the preoperative identification of peritoneal and distant metastases in patients with locally advanced gastric carcinoma. In intestinal and mixed-type tumours, the classification performance of the clinical model slightly improved with the addition of radiomic features, but this slight improvement does not outweigh the laborious radiomic analysis. Full article

Gastric carcinoma is generally considered to be a rare disease in dogs, carrying a grave prognosis. However, in the Tervueren and Groenendael varieties of the Belgian Shepherd dog breed, the disease is highly prevalent. While histopathology is the gold standard for diagnosing gastric carcinoma, there is no general consensus on the methods for histological classification in these cases. Biopsies of a group of 61 dogs with confirmed gastric carcinoma (45 Tervueren and 16 Groenendael) were examined and classified according to World Health Organization (WHO) and Laurén classifications. Kaplan–Meier curves were used to compare survival between the different subtypes and simple and multiple linear regression were used to analyse the association between age of onset and breed variant, sex, neuter status, location of the tumour, inflammation score, and Laurén and WHO classifications. Mean age at diagnosis was significantly different in Groenendael (10.1 ± 2.01) and Tervueren dogs (8.5 ± 1.90). The Laurén classification resulted in 29 (48%) diffuse- and 32 (52%) intestinal-type tumours. Applying the WHO classification resulted in 30 (49%) tubular carcinoma growth patterns and 31 (51%) others. Median survival time was significantly reduced for the diffuse type as compared to the intestinal type according to the Laurén classification, with the same median survival time results for tubular compared to non-tubular subtypes according to the WHO classification (median survival time of 61 vs. 182 days, respectively). Using the WHO and Lauren classification on tumour biopsies may help the practising clinician in the prognostication of gastric carcinoma in Tervueren and Groenendael dogs. Full article

Background and objectives: This study aims to elucidate the prognostic implications of Epstein–Barr virus (EBV) infection in gastric carcinomas (GCs) through a systematic review and meta-analysis. Materials and Methods: In total, 57 eligible studies and 22,943 patients were included in this meta-analysis. We compared the prognoses of EBV-infected and non-infected GC patients. The subgroup analysis was performed based on the study location, molecular classification, and Lauren’s classification. This study was checked according to the PRISMA 2020. The meta-analysis was performed using the Comprehensive Meta-Analysis software package. Results: EBV infection was found in 10.4% (95% confidence interval (CI) 0.082–0.131) of GC patients. The EBV-infected GC patients had a better overall survival compared with the EBV-non-infected GC patients (hazard ratio (HR) 0.890, 95% CI 0.816–0.970). In the subgroup analysis based on molecular classification, no significant differences were found between EBV+ and microsatellite instability and microsatellite stable (MSS)/EBV− subgroups (HR 1.099, 95% CI 0.885–1.364 and HR 0.954, 95% CI 0.872–1.044, respectively). In the diffuse type of Lauren’s classification, EBV-infected GCs have a better prognosis compared with the EBV-non-infected GCs (HR 0.400, 95% CI 0.300–0.534). The prognostic impact of EBV infection was found in the Asian and American subgroups but not in the European subgroup (HR 0.880, 95% CI 0.782–0.991, HR 0.840, 95% CI 0.750–0.941, and HR 0.915, 95% CI 0.814–1.028). Conclusions: EBV infection is a favorable survival factor for GCs. However, the prognostic implications of EBV infection in the new molecular classification are not clear. Full article

Introduction: 2–8% of all gastric cancer occurs at a younger age, also known as early-onset gastric cancer (EOGC). The aim of the present work was to use clinical registry data to classify and characterize the young cohort of patients with gastric cancer more precisely. Methods: German Cancer Registry Group of the Society of German Tumor Centers—Network for Care, Quality and Research in Oncology (ADT)was queried for patients with gastric cancer from 2000–2016. An approach that stratified relative distributions of histological subtypes of gastric adenocarcinoma according to age percentiles was used to define and characterize EOGC. Demographics, tumor characteristics, treatment and survival were analyzed. Results: A total of 46,110 patients were included. Comparison of different groups of age with incidences of histological subtypes showed that incidence of signet ring cell carcinoma (SRCC) increased with decreasing age and exceeded pooled incidences of diffuse and intestinal type tumors in the youngest 20% of patients. We selected this group with median age of 53 as EOGC. The proportion of female patients was lower in EOGC than that of elderly patients (43% versus 45%; p < 0.001). EOGC presented more advanced and undifferentiated tumors with G3/4 stages in 77% versus 62%, T3/4 stages in 51% versus 48%, nodal positive tumors in 57% versus 53% and metastasis in 35% versus 30% (p < 0.001) and received less curative treatment (42% versus 52%; p < 0.001). Survival of EOGC was significantly better (five-years survival: 44% versus 31% (p < 0.0001), with age as independent predictor of better survival (HR 0.61; p < 0.0001). Conclusion: With this population-based registry study we were able to objectively define a cohort of patients referred to as EOGC. Despite more aggressive/advanced tumors and less curative treatment, survival was significantly better compared to elderly patients, and age was identified as an independent predictor for better survival. Full article

Gastric cancer metastasis is a process in which the tumor microenvironment may carry significant influence. Helicobacter pylori (H. pylori) infection is well-established as a contributor to gastric carcinoma. However, the role that these bacteria and others may play in gastric carcinoma metastasis is a current focus of study. A review of the literature was conducted to elucidate the process by which gastric adenocarcinoma metastasizes, including its ability to utilize both the lymphatic system and the venous system to disseminate. Studies that investigate the tumor microenvironment at both the primary and secondary sites were assessed in detail. H. pylori and Mycoplasma hyorhinis (M. hyorhinis) were found to be important drivers of the pathogenesis of gastric adenocarcinoma by modifying various steps in cell metastasis, including epithelial–mesenchymal transition, cell migration, and cell invasion. H. pylori is also a known driver of MALT lymphoma, which is often reversible simply with the eradication of infection. M. hyorhinis has been implicated in gastric neoplasia via β-catenin stabilization and subsequent activation of the WNT-signaling pathway, promoting gastric cancer cell motility and inciting cancer progression. Fusobacterium nucleatum (F. nucleatum) and its association with worse prognosis in diffuse-type gastric adenocarcinoma are also reviewed. Recognition of the roles that bacteria play within the metastatic cascade is vital in gastrointestinal adenocarcinoma treatment and potential reoccurrence. Further investigation is needed to establish potential treatment for metastatic gastric carcinoma by targeting the tumor microenvironment. Full article

Gastric cancer (GC) is a major cause of cancer-related death worldwide. Patients with an aggressive subtype of GC, known as diffuse-type gastric carcinoma (DGC), have extremely poor prognoses. DGC is characterized by rapid infiltrative growth, massive desmoplastic stroma, frequent peritoneal metastasis, and high probability of recurrence. These clinical features and progression patterns of DGC substantially differ from those of other GC subtypes, suggesting the existence of specific oncogenic signals. The importance of gene amplification and the resulting aberrant activation of receptor tyrosine kinase (RTK) signaling in the malignant progression of DGC is becoming apparent. Here, we review the characteristics of RTK gene amplification in DGC and its importance in peritoneal metastasis. These insights may potentially lead to new targeted therapeutics. Full article

Background and aims. Signet ring cell (SRC) and poorly cohesive (PC) gastric carcinomas are morphologically similar but exhibit different biological behavior. We compared the clinical and molecular characteristics of SRC and PC carcinomas. Methods. Diffuse-type gastric cancer (GC) cases were classified into SRC carcinomas (>90% of SRCs), PC carcinomas (<10% of SRCs), and combined PC/SRC carcinomas (≤90% but ≥10% of SRCs). The gene expression patterns in SRC and PC carcinomas were examined by transcriptome and protein immunohistochemistry analyses, and diagnostic and prognostic biomarkers were identified. Results. SRC and PC carcinomas showed significantly different clinical behaviors but shared common RNA expression patterns. PC carcinomas showed an increased expression of genes related to cancer progression. Among genes differentially expressed between PC and SRC carcinomas, protein tyrosine phosphatase receptor type M (PTPRM) was overexpressed in PC and related to unfavorable clinical factors. Conclusion. We found that PC and SRC carcinomas had distinct clinical characteristics and should be classified as different carcinoma types. PTPRM was identified as a potential diagnostic and prognostic biomarker for PC carcinomas and could represent a potential therapeutic target. Full article

E-cadherin (E-cad) is a cell-adhesion molecule known for its tumor-invasion suppressor function. E-cad expression was examined immunohistochemically in a series of canine tissue samples, including normal gastric mucosa (NGM; n = 3), gastric carcinomas (GC; n = 33), adjacent non-neoplastic mucosa (NNM; n = 32), neoplastic emboli (n = 16) and metastatic lesions (n = 9). The relationship between E-cad expression and clinicopathological features were investigated. In NGM, epithelial cells showed strong latero-lateral membranous expression of E-cad, and this pattern was considered normal. The membranous staining was preserved in all specimens of NNM (100%), whereas abnormal E-cad expression was found in 87.9% of the GCs. A marked difference in E-cad expression was observed between normal and malignant tissues (p < 0.0002). Abnormal E-cad expression was significantly more frequent in poorly/undifferentiated carcinomas (96%) and diffuse (95%) and indeterminate carcinomas (100%) than in well-differentiated/intestinal ones (62.5%; p = 0.0115 and p = 0.0392, respectively). There was significant association between abnormal E-cad expression and the depth of invasion (p = 0.0117), and the presence neoplastic emboli (p = 0.0194). No statistically significant differences in E-cad expression were observed concerning tumor location, histological type according to WHO classification, and presence of metastatic lesions. Therefore, deregulation of E-cad expression may play a role in canine gastric carcinogenesis and in tumor progression; moreover, it might be a prognostic tool for canine gastric cancer. Full article

Malignant tumours are traditionally classified according to their organ of origin and whether they are of epithelial (carcinomas) or mesenchymal (sarcomas) origin. By histological appearance the site of origin may often be confirmed. Using same treatment for tumours from the same organ is rational only when there is no principal heterogeneity between the tumours of that organ. Organ tumour heterogeneity is typical for the lungs with small cell and non-small cell tumours, for the kidneys where clear cell renal carcinoma (CCRCC) is the dominating type among other subgroups, and in the stomach with adenocarcinomas of intestinal and diffuse types. In addition, a separate type of neuroendocrine tumours (NETs) is found in most organs. Every cell type able to divide may develop into a tumour, and the different subtypes most often reflect different cell origin. In this article the focus is on the cells of origin in tumours arising in the stomach and kidneys and the close relationship between normal neuroendocrine cells and NETs. Furthermore, that the erythropoietin producing cell may be the cell of origin of CCRCC (a cancer with many similarities to NETs), and that gastric carcinomas of diffuse type may originate from the ECL cell, whereas the endodermal stem cell most probably gives rise to cancers of intestinal type. Full article

The peritoneum is a common metastatic site in gastric cancer. This systematic review provides an overview of the incidence, risk factors and survival of synchronous peritoneal metastases from gastric cancer. A systematic search was performed to identify studies wherein the incidence, risk factors and survival of gastric cancer with peritoneal metastases were investigated. Of all 38 potentially eligible studies, 17 studies were included based on the eligibility criteria. The incidence of synchronous gastric peritoneal metastases was reviewed for population-based studies (10–21%), for observational cohort studies (2–15%) and for surgical cohort studies (13–40%). Potential risk factors for synchronous gastric peritoneal metastases were younger age, non-cardia gastric cancer, female sex, signet ring cell carcinoma, diffuse type histology or linitis plastica, T4 stage, Hispanic ethnicity and more than one metastatic location. Synchronous peritoneal metastases are commonly diagnosed in patients with gastric cancer with an incidence up to 21% in recent population-based studies. Furthermore, prognosis of patients with gastric peritoneal metastases is poor with median overall survival ranging from 2 to 9 months. The high incidence and poor prognosis require intensive research on diagnostic features and effective treatment options to improve survival. Full article

Fertility sparing management of cancer is one of the main components of quality-of-life issues. Early-stage cervical cancer, frequently diagnosed in women of reproductive age, can potentially be treated conservatively. However, some rare histological types of cervical cancer present with aggressive clinical behavior. Particularly, in the newly introduced concept of gastric-type endocervical carcinoma, fertility sparing management is ‘a priori’ not recommended. Even so, this issue remains undocumented. For this reason, a selected review of the current literature on gastric type endocervical carcinoma was carried out through PubMed. The keywords included “gastric-type cervical cancer”, “gastric-type endocervical carcinoma”, “conservative surgery”, “conservative treatment”, “fertility sparing surgery”, “radical trachelectomy”, “laparoscopic trachelectomy”, “robotic trachelectomy”, “laparotomic trachelectomy”, “abdominal trachelectomy”, “trachelectomy”, “neoadjuvant chemotherapy”, “conisation”, and “cone resection”. A search in the European Network on Cancer, Infertility and Pregnancy (INCIP) database was performed. The rarity of gastric-type endocervical carcinoma does not allow for conclusions on fertility sparing management with solid evidence. However, diffuse character of the disease and aggressive clinical behavior contraindicate a conservative treatment in young women with gastric type cervical cancer. Full article