Introduction Gastric carcinoma is a significant global health concern, known for its high mortality rate. HER-2 overexpression is observed in a notable proportion of gastric carcinoma and is associated with a worse prognosis. However, HER-2 expression enables targeting the protein by monoclonal antibodies that improve overall survival in HER-2-positive gastric cancers. This study aims to evaluate the HER-2 expression in gastric and gastroesophageal carcinomas. Materials and methods This observational study was conducted in the Department of Pathology, involving 60 endoscopic biopsy and resection specimens of gastric and gastroesophageal carcinomas. HER-2 expression was assessed by immunohistochemistry (IHC) based on the Trastuzumab for GAstric Cancer (ToGA) trial\'s scoring system. The primary outcome was HER-2 status, with statistical analysis performed to evaluate associations with various clinicopathological parameters. Results Among 60 cases, 26 (43.3%) showed HER-2 positivity. HER-2 positivity was significantly (p=0.004) associated with age, being higher in 20-39 years and ≥80 years age groups. Gender and tumor location were not significantly associated with HER-2 positivity. Moderate and poorly differentiated carcinomas exhibited higher HER-2 positivity. Histological types, tubular adenocarcinoma, and papillary adenocarcinoma showed significant (p=0.01) association with HER-2 positivity compared to other types. Conclusion HER-2 status assessment is crucial in managing gastric and gastroesophageal carcinomas. HER-2 positivity is notably higher in certain age groups and histological types particularly tubular and papillary adenocarcinoma, and in moderately to poorly differentiated carcinomas. These insights can aid in selecting appropriate gastric and gastroesophageal carcinomas that warrant HER-2 testing on IHC. Identifying gastric and gastroesophageal carcinomas that show HER2 expression may highlight potential candidates for targeted therapy.

UNASSIGNED: Gastric cancer (GC) is one of the most common tumors. There were several classifications of GC recently. The value of Lauren classification in evaluating the prognosis after radical gastrectomy was still unclear and the prognosis of gastric cancer remained relatively poor in the absence of prognostic biomarkers. This study aimed to explore microRNA (miRNA) in the prognosis of GC with different Lauren classification.
UNASSIGNED: A retrospective study of 1144 patients was performed in this study. Quantificational reverse transcription-PCR (qRT-PCR) was used to examine the expression of miRNAs. Univariate and multivariate analysis were performed to evaluate prognosis value of Lauren classification.
UNASSIGNED: Total 1144 GC patients were recruited in this cohort, including 302 diffuse type (26.4%), 436 intestinal type (38.1%) and 406 mixed type (35.5%) GC. Multivariate analysis showed that Lauren classification, patients\' age, tumor size, tumor infiltrating depth, vascular nerve infiltrating and metastatic lymph nodes ration were significantly correlated with GC patients\' OS and DFS. The miR-141-3p, miR-200b-3p and miR-133a-5p were significantly down-regulated in diffuse type compared to intestinal type GC tissues, the miR-105-5p had significant lower expression in diffuse type compared with intestinal type and mixed type GC tissues. As a consequence of univariate analysis, low miR-141-3p in diffuse type GC showed significant worse OS and DFS than high miR-141-3p.
UNASSIGNED: Lauren classification was an independent prognostic factor in GC. MiR-141-3p was an independent prognostic factor and a promising prognostic biomarker in Lauren classification GC.

BACKGROUND: Numerous studies have demonstrated a correlation between p53 overexpression and diminished survival in gastric cancer patients. However, conflicting findings exist, and we hypothesize that these discrepancies arise from the cancer\'s complexity and heterogeneity, coupled with a lack of consensus on aberrant p53 expression.
METHODS: We enrolled a cohort of 187 patients with surgically resected gastric cancer. Patient categorization was based on Epstein-Barr virus (EBV), microsatellite instability (MSI), and Lauren classification (intestinal, diffuse and mixed). Utilizing an incremental algorithm, we evaluated p53 immunohistochemical (IHC) patterns in all 187 cases, while next-generation sequencing was successfully performed on 152 cases to identify TP53 mutations (mutTP53).
RESULTS: MutTP53 was identified in 32 % of the 152 cases, comprising 36 missense, 5 nonsense, and 7 frameshift alterations. Missense mutations predominantly correlated with p53 overexpression, while nonsense and frameshifting alterations related to null expression. Trial calculations indicated that null expression and a p53 IHC cutoff at >40 % offered the best prediction of mutTP53 (kappa coefficient, 0.427), with the highest agreement (0.524) observed in diffuse type and the lowest (0.269) in intestinal type. Null expression and a p53 IHC cutoff at >10 %, but not mutTP53 per se, provided the optimal prediction of survival outcome (p = 0.043), particularly in diffuse type (p = 0.044). Multivariate analysis showed that aberrant p53 IHC expression was not an independent prognostic factor.
CONCLUSIONS: P53 IHC patterns are predictive biomarkers for mutTP53 and gastric cancer outcomes, where a prerequisite involves a nuanced approach considering cutoff values and molecular-histologic subtyping.

UNASSIGNED: The prognostic significance of Lauren\'s classification in elderly early gastric cancer (EGC) patients remains largely unknown. We aim to investigate the characteristics and clinical implications of Lauren\'s classification in elderly EGC patients.
UNASSIGNED: Patients were collected from the Surveillance, Epidemiology, and End Results (SEER) database based on the inclusion and exclusion criteria. Univariate and multivariate Cox regression, propensity score matching, inverse-probability-weighted analysis, and propensity-score adjustment were utilized to evaluate the association between Lauren\'s classification and cancer-specific survival (CSS) in elderly EGC patients. Stratification and interaction analyses were used to reveal the effects of confounding factors on the association between Lauren\'s classification and CSS.
UNASSIGNED: The diffuse type (median, 41.0 months) showed a similar survival (37.0 months), and was mainly distributed in female group (62.5% vs. 42.2%) with poorly differentiated or undifferentiated components (89.1% vs. 27.0%) compared with intestinal type in elderly EGC patients. Analyses of univariate and multivariate Cox regression, propensity score matching, inverse-probability-weighted analysis, and propensity-score adjustment showed that Lauren\'s classification was not significantly CSS in elderly EGC patients (P>0.05). Subgroup and interaction analyses confirmed the stability of the results.
UNASSIGNED: Diffuse type was mainly distributed in female patients with more poorly differentiated/undifferentiated components and similar prognosis compared with intestinal type in age 75 and older EGC patients. No significant association was observed between diffuse type and CSS of the elderly EGC patients.

OBJECTIVE: This study aims to investigate the impact of sex on outcome measures stratified by histological subtype in patients with resectable gastric cancer (GC).
METHODS: A post-hoc analysis of the CRITICS-trial, in which patients with resectable GC were treated with perioperative therapy, was performed. Histopathological characteristics and survival were evaluated for males and females stratified for histological subtype (intestinal/diffuse). Additionally, therapy-related toxicity and compliance were compared.
RESULTS: Data from 781 patients (523 males) were available for analyses. Female sex was associated with a distal tumor localization in intestinal (p = 0.014) and diffuse tumors (p < 0.001), and younger age in diffuse GC (p = 0.035). In diffuse GC, tumor-positive resection margins were also more common in females than males (21% vs. 10%; p = 0.020), specifically at the duodenal margin. During preoperative chemotherapy, severe toxicity occurred in 327 (63%) males and 184 (71%) females (p = 0.015). Notwithstanding this, relative dose intensities were not significantly different between sexes.
CONCLUSIONS: Positive distal margin rates were higher in females with diffuse GC, predominantly at the duodenal site. Females also experience more toxicity, but this neither impacts dose intensities nor surgical resection rates. Clinicians should be aware of these different surgical outcomes when treating males and females with GC.

In the era of individualized gastric cancer (GC) treatment, accurate determination of histological subtype becomes increasingly relevant. As yet, it is unclear whether preoperative chemotherapy may affect the histological subtype. The aim of this study was to assess concordance in histological subtype between pretreatment biopsies and surgical resection specimens before and after the introduction of perioperative treatment.
Histological subtype was centrally determined in paired GC biopsies and surgical resection specimens of patients treated with either surgery alone (SA) in the Dutch D1/D2 study or with preoperative chemotherapy (CT) in the CRITICS trial. The histological subtype as determined in the resection specimen was considered the gold standard. Concordance rates and sensitivity and specificity of intestinal, diffuse, mixed, and \"other\" subtypes of GC were analyzed.
In total, 105 and 515 pairs of GC biopsies and resection specimens of patients treated in the SA and CT cohorts, respectively, were included. Overall concordance in the histological subtype was 72% in the SA and 74% in the CT cohort and substantially higher in the diffuse subtype (83% and 86%) compared to the intestinal (70% and 74%), mixed (21% and 33%) and \"other\" subtypes (54% and 54%). In the SA cohort, sensitivities and specificities were 0.88 and 0.71 in the intestinal, 0.67 and 0.93 in the diffuse, 0.20 and 0.98 in the mixed, and 0.50 and 0.93 in the \"other\" subtypes, respectively.
Our results suggest that accurate determination of histological subtype on gastric cancer biopsies is suboptimal but that the impact of preoperative chemotherapy on histological subtype is negligible.

OBJECTIVE: To investigate the value of a radiomics model based on dual-energy computed tomography (DECT) venous-phase iodine map (IM) and 120 kVp equivalent mixed images (MIX) in predicting the Lauren classification of gastric cancer.
METHODS: A retrospective analysis of 240 patients undergoing preoperative DECT and postoperative pathologically confirmed gastric cancer was done. Training sets (n = 168) and testing sets (n = 72) were randomly assigned with a ratio of 7:3. Patients are divided into intestinal and non-intestinal groups. Traditional features were analyzed by two radiologists, using logistic regression to determine independent predictors for building clinical models. Using the Radiomics software, radiomics features were extracted from the IM and MIX images. ICC and Boruta algorithm were used for dimensionality reduction, and a random forest algorithm was applied to construct the radiomics model. ROC and DCA were used to evaluate the model performance.
RESULTS: Gender and maximum tumor thickness were independent predictors of Lauren classification and were used to build a clinical model. Separately establish IM-radiomics (R-IM), mixed radiomics (R-MIX), and combined IM + MIX image radiomics (R-COMB) models. In the training set, each radiomics model performed better than the clinical model, and the R-COMB model showed the best prediction performance (AUC: 0.855). In the testing set also, the R-COMB model had better prediction performance than the clinical model (AUC: 0.802).
CONCLUSIONS: The R-COMB radiomics model based on DECT-IM and 120 kVp equivalent MIX images can effectively be used for preoperative noninvasive prediction of the Lauren classification of gastric cancer.
UNASSIGNED: The radiomics model based on dual-energy CT can be used for Lauren classification prediction of preoperative gastric cancer and help clinicians formulate individualized treatment plans and assess prognosis.

Background: We explored whether a model based on contrast-enhanced computed tomography radiomics features and clinicopathological factors can evaluate preoperative lymphovascular invasion (LVI) in patients with gastric cancer (GC) with Lauren classification. Methods: Based on clinical and radiomic characteristics, we established three models: Clinical + Arterial phase_Radcore, Clinical + Venous phase_Radcore and a combined model. The relationship between Lauren classification and LVI was analyzed using a histogram. Results: We retrospectively analyzed 495 patients with GC. The areas under the curve of the combined model were 0.8629 and 0.8343 in the training and testing datasets, respectively. The combined model showed a superior performance to the other models. Conclusion: CECT-based radiomics models can effectively predict preoperative LVI in GC patients with Lauren classification.

OBJECTIVE: To develop a combined radiomics nomogram based on computed tomography (CT) images and clinical features to preoperatively distinguish Lauren\'s diffuse-type gastric cancer (GC) from intestinal-type GC.
METHODS: Ninety-five patients with Lauren\'s intestinal or diffuse-type GC confirmed by postoperative pathology had their preoperative clinical information and dynamic contrast CT images retrospectively analyzed and were subdivided into training and test groups in a 7:3 ratio. To select the optimal features and construct the radiomic signatures, we extracted, filtered, and minimized the radiomic features from arterial phase (AP) and venous phase (VP) CT images. We constructed four models (clinical model, AP radiomics model, VP radiomics model, and radiomics-clinical model) to assess and compare their predictive performance between the intestinal- and diffuse-type GC. Receiver-operating characteristic (ROC) curve, area under the ROC curve (AUC), and the DeLong test were used for assessment and comparison. In this study, radiomic nomograms integrating combined radiomic signatures and clinical characteristics were developed.
RESULTS: Compared to the AP radiomics model, the VP radiomics model had better performance, with an AUC of 0.832 (95% confidence interval [CI], 0.735, 0.929) in the training cohort and 0.760 (95% CI 0.580, 0.940) in the test cohort. Among the combined models that assessed Lauren\'s type GC, the model including age and VP radiomics showed the best performance, with an AUC of 0.849 (95% CI 0.758, 0.940) in the training cohort and 0.793 (95% CI 0.629, 0.957) in the test cohort.
CONCLUSIONS: Nomogram incorporating radiomic signatures and clinical features effectively differentiated Lauren\'s diffuse-type from intestinal-type GC.

UNASSIGNED: Fat mass and obesity-associated protein (FTO) and AlkB homolog 1 (ALKBH1) are m6A demethylases that have been demonstrated to be associated with the overall survival of patients with gastric cancer (GC). This study investigates the influence of genetic variants of FTO and ALKBH1 on susceptibility to GC.
UNASSIGNED: Potentially functional single nucleotide polymorphisms (SNPs) of FTO and ALKBH1 were genotyped in 419 patients with GC and 569 healthy controls by Kompetitive allele-specific PCR.
UNASSIGNED: The AG and AG/AA variants of FTO rs2287142 were significantly associated with a decreased GC risk (for AG/AA vs GG: adjusted OR = 0.73, p = 0.020). The GA and GA/GG variants of ALKBH1 rs1076496 were closely correlated with an increased risk of GC in people aged ≥ 55 years (for GA/GG vs AA: adjusted OR = 1.51, p = 0.041) but showed a decreasing tendency of risk of GC in people aged <55 years (adjusted OR = 0.85, p = 0.444). FTO rs2287142 and ALKBH1 rs1076496 conformed to the principle of a dominant model. FTO haplotype rs1421091-rs1421092-rs2287142-rs9939609 CTAT was closely associated with a lower risk of total GC (adjusted OR = 0.62, p = 0.023), while CTGA was linked with an increased risk of intestinal GC (adjusted OR = 2.51, p = 0.005). ALKBH1 rs1048147-rs1076496-rs11159286 CAC haplotype was significantly associated with a decreased risk of GC in people aged ≥ 55 years (adjusted OR = 0.41, p = 0.008). The FTO rs2287142-rs9939609 AG/AA-TT combination was associated with a decreased risk of GC only in the presence of rs1421091 TC/TT (adjusted OR = 0.70, p = 0.047), demonstrating that these FTO SNPs might have a cooperative effect on susceptibility to GC.
UNASSIGNED: FTO and ALKBH1 SNPs may have predictive value in evaluating susceptibility to GC with differing age or Lauren classification.