MSI-H/dMMR

EBV-GC is characterized by distinct clinicopathological and molecular features. Pathological examination, immunophenotyping, and NGS provide significant value for diagnosis and therapeutic direction.

After adjustment for clinical covariates, US and Japanese gastric cancers exhibit comparable genomic landscapes and survival, supporting the relevance of clinical trial data across geographic settings.

Right-sided colon cancers with MSI-H status were associated with larger tumor size, mucinous histology, and poor differentiation but did not significantly affect survival outcomes. Postoperative CEA monitoring provides critical prognostic information. Further large-scale studies are required to confirm these findings and refine therapeutic approaches.

MLH1ph ECs represent a higher-risk molecular subgroup with significantly poorer survival. Our findings support routine MLH1ph testing when MLH1/PMS2 protein loss is identified. Improved recognition of this subgroup is crucial for refining molecular risk stratification and will enable more personalized and effective oncologic management strategies based on tumour biology.

Surgical stage remains a strong prognostic factor across molecular subtypes and should be considered alongside molecular classification when tailoring adjuvant treatment in EC.

In esophageal tumors, adjuvant nivolumab is used. Among HER2-positive patients, adding pembrolizumab to trastuzumab and chemotherapy - in PDL1 CPS ≥1 cases - has become a new standard. A special mention must be made of MSI-H tumors, in which immunotherapy is highly effective, and adjuvant chemotherapy is not recommended according to current guidelines.

By 2025, immunotherapy has become the therapeutic basis for UC and RCC, both in metastatic and curative treatments. In PCa and TGCT, immunotherapy options remain in the experimental phase, but research is ongoing with new combinations and biomarker-driven strategies.

In conclusion, quantitative GC-related histology of nrLNs can serve as a prognostic indicator for MSI-H CRC. Our findings suggest that GC-activated nrLNs may represent B cell-mediated antitumor immunity, independent of tumor-infiltrating T cells and tumor-intrinsic molecular characteristics.

Although outcomes varied depending on the PEM treatment duration and the medical cost setting after disease progression in the SoC group, PEM was suggested to be more cost-effective than SoC at the reference willingness-to-pay threshold of JPY15 million per QALY in Japan.

We established a DRRG-based prognostic model for CRC and uncovered their links to metabolic regulation, immune infiltration, and metastasis. These findings highlight DRRGs as potential biomarkers and therapeutic targets and suggest that DR-mimicking strategies may benefit CRC management.

This review provides a comprehensive overview of the evolving therapeutic landscape of GEC. It emphasizes the growing role of precision medicine and the integration of emerging clinical data into practice.

In conclusion, discordance between IHC- and NGS-based MMR/MSI detection is primarily attributable to MSH6 loss with MSH3 compensation and MLH1 promoter methylation. Recognizing these mechanisms is essential for accurate molecular subtyping and clinical decision-making in EC.