Background Cholesterol is crucial for tumor immune microenvironment (TIME) remodeling. Serum lipoprotein cholesterol is closely associated with gastric cancer (GC) progression, but whether it affects TIME remodeling is unknown. Methods GC patients with differential serum high-density lipoprotein (HDL) or low-density lipoprotein (LDL) cholesterol levels were collected. After balancing the baseline, immunohistochemical staining was performed on serial whole-tissue sections to detect B-cell and T-cell subsets, macrophages, and PD-L1. Features of tertiary lymphoid structures (TLSs) and the extra-TLS zone, including TLS distribution and maturation, immune cell density, and PD-L1 expression, were measured by annotating TLSs or regions of interest (ROIs) in the extra-TLS zone. Results A total of 9,192 TLSs and over 300 ROIs from 61 patients were measured. Compared to HDL-normal patients, HDL-low patients had a decreased secondary-TLS fraction or density but an elevated NK-cell density in the extra-TLS zone. Compared to LDL-normal patients, LDL-low patients had a higher ratio of PD-1 + T follicular helper cells to CD20 + B cells in TLSs, a higher ratio of PD-1 + T cells to CD8 + T cells and increased PD-1 + T-cell density in the extra-TLS zone. Different correlations were found in groups with differential HDL or LDL levels. Cell dynamics in the immune response were weaker in patients with low lipoprotein cholesterol. TLS parameters reached their peak earlier than those of the extra-TLS zone along with tumor progression. Conclusion Low serum lipoprotein cholesterol caused adverse effects on antitumor immunity in GC. Lipid management or immunometabolic drugs deserve more attention.

Purpose: Pleomorphic xanthoastrocytoma (PXA) is an uncommon astrocytoma that tends to occur in children and young adults and has a relatively favorable prognosis. The 2021 WHO classification of tumors of the central nervous system (CNS WHO), 5th edition, rates PXAs as grade 2 and grade 3. The histological grading was based on mitotic activity (≥2.5 mitoses/mm2). This study specifically evaluates the clinical, morphological, and, especially, the molecular characteristics of grade 2 and 3 PXAs. Methods: Between 2003 and 2021, we characterized 53 tumors with histologically defined grade 2 PXA (n = 36, 68%) and grade 3 PXA (n = 17, 32%). Results: Compared with grade 2 PXA, grade 3 PXA has a deeper location and no superiority in the temporal lobe and is more likely to be accompanied by peritumoral edema. In histomorphology, epithelioid cells and necrosis were more likely to occur in grade 3 PXA. Molecular analysis found that the TERT promoter mutation was more prevalent in grade 3 PXA than in grade 2 PXA (35% vs. 3%; p = 0.0005) and all mutation sites were C228T. The cases without BRAF V600E mutation or with necrosis in grade 3 PXA had a poor prognosis (p = 0.01). Conclusion: These data define PXA as a heterogeneous astrocytoma. Grade 2 and grade 3 PXAs have different clinical and histological characteristics as well as distinct molecular profiles. TERT promoter mutations may be a significant genetic event associated with anaplastic progression. Necrosis and BRAF V600E mutation play an important role in the prognosis of grade 3 PXA.

Background:The distribution of mucin phenotypes and its relationship with clinicopathological features in early differentiated gastric adenocarcinomas among the Chinese cohort is unknow. We aim to investigate the mucin phenotypes and analyze the relationship between mucin phenotypes and clinicopathological features, especially the biological behavior, in early differentiated gastric adenocarcinomas from endoscopic specimens in a Chinese cohort.Methods:Immunohistochemical staining of CD10, MUC2, MUC5AC, MUC6 was performed in 257 patients with early differentiated gastric adenocarcinomas. Tumor location, gross type, tumor size, histological type, depth of invasion, lymphovascular invasion, mucosal background and other clinicopathological parameters were evaluated. Analyzed the relationship between mucin phenotypes and clinicopathological features through chi-square test.ResultsThe incidence of ໿ gastric-, gastrointestinal-, intestinal- and null-phenotype was 21%, 56%, 20% and 3% respectively. The mucin phenotypes were related with histology classification (P༜0.05). The proportion of gastric-phenotype became greater during the transition from differentiated to undifferentiated (P༜0.05). Complete intestinal metaplasia in gastric- and intestinal-phenotype was higher than gastrointestinal-phenotype (P༜0.05). Those mixed with poorly differentiated adenocarcinoma were mainly of gastric-phenotype, which was significantly higher than that of purely differentiated tubular adenocarcinoma (P < 0.05), and the depth of infiltration of mixed type was deeper (P < 0.05). Neither recurrence nor metastasis were detected.ConclusionsThe mucin phenotype of early differentiated gastric adenocarcinoma is of clinical implication, and gastric-phenotype has aggressive biological behavior in early differentiated gastric cancers, especially in those mixed with poorly differentiated adenocarcinoma or papillary adenocarcinoma component.