Rapidly and Slowly Growing Lineages in Chromosomal Instability-Type Gland-Forming Gastric Carcinomas as Revealed by Multisampling Analysis of DNA Copy-Number Profile.

BACKGROUND: To examine whether gastric carcinoma (GC) with chromosomal instability (CIN-type GC), the largest category in the Cancer Genome Atlas classification, consists of a single genetic lineage, we conducted a multisampling analysis of genomic DNA copy-number profile. METHODS: We performed array-based comparative genomic hybridization using formalin-fixed paraffin-embedded tissues from 54 gland-forming GCs containing a total of 106 DNA samples from mucosal, extramucosal invasive, and lymph node lesions. Microarray data were analyzed by unsupervised hierarchical clustering and penetrance plots. Epstein-Barr virus infection status and mismatch repair (MMR) enzyme-silencing/p53/mucin expression were examined by in situ hybridization and immunohistochemistry, respectively. RESULTS: The samples examined were divided into gain-rich cluster A and loss-rich cluster B, which were different in tumor locus and patient age. The T1/T2-4 ratio, the frequency of small cancers (diameter ≤2-4 cm), and intestinal mucin expression were higher in cluster B than in cluster A, but there were no significant differences in the frequencies of MMR silencing, mutant p53 pattern, and lymph node metastasis between the 2 clusters. CONCLUSIONS: We demonstrated that CIN-type GC could be categorized into 2 genetic lineages which are different in terms of rapidity of local extension but similar in terms of nodal metastasis risk.

Endoscopic characteristics and performance of WASP classification in the diagnosis of colorectal sessile-serrated lesions in Vietnamese patients.

Background/Aims: Sessile-serrated lesions (SSLs) are challenging to detect due to their typically subtle appearance. The Workgroup serrAted polypS and Polyposis (WASP) classification was developed to diagnose SSLs endoscopically. This study aimed to evaluate the endoscopic characteristics of SSLs and the performance of the WASP classification in the Vietnamese population. Methods: This cross-sectional study was carried out on patients with lower gastrointestinal symptoms who underwent colonoscopy at a Vietnamese tertiary hospital. Univariate and multivariate analyses were performed to identify endoscopic features associated with SSLs. The performance of the WASP classification for diagnosing SSLs was assessed, and SSLs were diagnosed according to the 2019 World Health Organization (WHO) criteria. Results: There were 2489 patients, with a mean age of 52.1 ± 13.1 years and a female-to-male ratio of 1:1.1. A total of 121 specimens from 105 patients were diagnosed with SSLs. According to multivariate analysis, the endoscopic features significantly associated with SSLs were proximal location (odds ratio [OR]: 2.351; 95% confidence interval [CI]: 1.475-3.746), size >5 mm (OR: 2.447; 95% CI: 1.551-3.862), flat morphology (OR: 2.781; 95% CI: 1.533-5.044), irregular shape (OR: 4.516; 95% CI: 2.173-9.388), varicose microvascular vessels (OR: 5.030; 95% CI: 2.657-9.522), and dark spots inside the crypts (OR: 5.955; 95% CI: 3.291-10.776). The accuracy of the WASP classification for diagnosing SSLs was 94.0% (95% CI: 92.8%-95.0%). Conclusion: Proximal location, size >5 mm, flat morphology, irregular shape, varicose microvascular vessels, and dark spots inside the crypts were significantly associated with SSLs. The WASP classification had high accuracy in the diagnosis of SSLs.

Prevalence, risk factors, and BRAF mutation of colorectal sessile serrated lesions among Vietnamese patients.

BACKGROUND: Sessile serrated lesions (SSLs) are considered precancerous colorectal lesions that should be detected and removed to prevent colorectal cancer. Previous studies in Vietnam mainly investigated the adenoma pathway, with limited data on the serrated pathway. AIM: To evaluate the prevalence, risk factors, and BRAF mutations of SSLs in the Vietnamese population. METHODS: This is a cross-sectional study conducted on patients with lower gastrointestinal symptoms who underwent colonoscopy at a tertiary hospital in Vietnam. SSLs were diagnosed on histopathology according to the 2019 World Health Organization classification. BRAF mutation analysis was performed using the Sanger DNA sequencing method. The multivariate logistic regression model was used to determine SSL-associated factors. RESULTS: There were 2489 patients, with a mean age of 52.1 ± 13.1 and a female-to-male ratio of 1:1.1. The prevalence of SSLs was 4.2% [95% confidence interval (CI): 3.5-5.1]. In the multivariate analysis, factors significantly associated with SSLs were age ≥ 40 [odds ratio (OR): 3.303; 95%CI: 1.607-6.790], male sex (OR: 2.032; 95%CI: 1.204-3.429), diabetes mellitus (OR: 2.721; 95%CI: 1.551-4.772), and hypertension (OR: 1.650, 95%CI: 1.045-2.605). The rate of BRAF mutations in SSLs was 35.5%. CONCLUSION: The prevalence of SSLs was 4.2%. BRAF mutations were present in one-third of SSLs. Significant risk factors for SSLs included age ≥ 40, male sex, diabetes mellitus, and hypertension.

Diagnostic performance of the Japanese Narrow-band imaging expert team classification system using dual focus magnification in real-time Vietnamese setting.

The JNET classification, combined with magnified narrowband imaging (NBI), is essential for predicting the histology of colorectal polyps and guiding personalized treatment strategies. Despite its recognized utility, the diagnostic efficacy of JNET classification using NBI with dual focus (DF) magnification requires exploration in the Vietnamese context. This study aimed to investigate the diagnostic performance of the JNET classification with the NBI-DF mode in predicting the histology of colorectal polyps in Vietnam. A cross-sectional study was conducted at the University Medical Center in Ho Chi Minh City, Vietnam. During real-time endoscopy, endoscopists evaluated the lesion characteristics and recorded optical diagnoses using the dual focus mode magnification according to the JNET classification. En bloc lesion resection (endoscopic or surgical) provided the final pathology, serving as the reference standard for optical diagnoses. A total of 739 patients with 1353 lesions were recruited between October 2021 and March 2023. The overall concordance with the JNET classification was 86.9%. Specificities and positive predictive values for JNET types were: type 1 (95.7%, 88.3%); type 2A (81.4%, 90%); type 2B (96.6%, 54.7%); and type 3 (99.9%, 93.3%). The sensitivity and negative predictive value for differentiating neoplastic from non-neoplastic lesions were 97.8% and 88.3%, respectively. However, the sensitivity for distinguishing malignant from benign neoplasia was lower at 64.1%, despite a specificity of 95.9%. Notably, the specificity and positive predictive value for identifying deep submucosal cancer were high at 99.8% and 93.3%. In Vietnam, applying the JNET classification with NBI-DF demonstrates significant value in predicting the histology of colorectal polyps. This classification guides treatment decisions and prevents unnecessary surgeries.

Adenocarcinoma arising in multiple hyperplastic polyps in a patient with Helicobacter pylori infection and hypergastrinemia during long-term proton pump inhibitor therapy.

We report a case of developing multiple adenocarcinoma foci in multiple hyperplastic polyps in a patient with Helicobacter pylori infection and hypergastrinemia during long-term proton pump inhibitor (PPI) therapy. A 57-year-old man, who was undergoing hemodialysis for chronic renal failure, underwent an upper gastrointestinal endoscopy to elucidate the cause of anemia. Atrophic gastritis with H. pylori infection and multiple adenocarcinoma foci in multiple hyperplastic polyps were found in the endoscopic and histological examinations. Enterochromaffin-like micronests and parietal cell protrusion in the background of the polyps suggested the existence of hypergastrinemia. The serum gastrin level was markedly high-10,206 pg/ml (normal range 37-172 pg/ml). The cause of this marked hypergastrinemia was not autoimmune gastritis and gastrinoma. After discontinuing PPI therapy and successful eradication of H. pylori, the serum gastrin level decreased to normal range. These findings indicate that hypergastrinemia may be caused by long-term PPI therapy in patients with H. pylori infection. This case suggests that hypergastrinemia may mediate gastric carcinogenesis in patients with H. pylori infection.

Progression risk assessments of individual non-invasive gastric neoplasms by genomic copy-number profile and mucin phenotype.

BACKGROUND: Early detection and treatment of non-invasive neoplasms can effectively reduce the incidence of advanced gastric carcinoma (GC), but only when the lineage is continuous between non-invasive and advanced tumours. Although a fraction of non-invasive neoplasms progress to invasive GC, it is difficult to identify individual progression-prone non-invasive neoplasms. To classify non-invasive gland-forming gastric neoplasms into clusters of different levels of progression risk, we applied mucin phenotyping and genomic DNA microarray analyses to intramucosal gland-forming gastric neoplasms. METHODS: Formalin-fixed, paraffin-embedded tissues from 19 non-invasive and 24 invasive gland-forming neoplasms were obtained via endoscopic submucosal dissection or surgical excision. According to the Vienna classification, intramucosal neoplasms were classified as low-grade or high-grade non-invasive neoplasms (LGNs [category 3] and HGNs [category 4], respectively) or invasive carcinomas (intramucosal GCs and mucosal parts of submucosal or deeper GCs [category 5]). Neoplastic lesions were characterized by mucin phenotypes determined using monoclonal antibodies against MUC2, MUC5AC, MUC6, and CD10. Genomic DNA samples from mucosal neoplasms were subjected to array-based comparative genomic hybridization and subsequent unsupervised, hierarchical clustering with selected large-sized genes. RESULTS: There was no significant difference in mucin phenotype between HGNs/LGNs and invasive carcinomas. The clustering classified samples into stable, unstable, and intermediate. The histological tumour grade or mucin phenotype of non-invasive neoplasms did not correlate with the clustering results. Each cluster may represent an independent lineage of different outcome because the size distribution of non-invasive tumours among the 3 clusters almost overlapped. In contrast, the unstable cluster alone included invasive carcinomas. CONCLUSIONS: These findings suggest that the outcome of individual tumours is not stochastically determined but can be predicted from the genomic copy-number profile even at the non-invasive stage. Non-invasive neoplasms of the unstable clusters, which accounted for 21% of non-invasive neoplasms, may progress to invasive carcinomas, whereas those of stable cluster may not.