PMS2 (PMS1 protein homolog 2)

For CRC patients with variants in high-risk LS genes, extended resection can significantly reduce the risk of metachronous CRC but does not lengthen overall survival. Segmental resection with close endoscopic surveillance can be a reasonable alternative, given the opportunity for repeat surgery and/or immune checkpoint blockade.

High FOLR1 expression identifies a biologically aggressive subset of gastric adenocarcinoma with inferior RFS and independent prognostic value. Its concurrent association with PD-L1 and HER2, together with relative absence in dMMR tumors, supports biomarker-guided strategies that consider FOLR1 alongside HER2 and PD-L1, and provides a rationale to explore FOLR1-targeted therapies in selected patients.

HER3 positivity was observed in 3/5 of the intermediate MutL cases and HER2 positivity in only one. MMR deficiency and potential MSI-H status were identified to be relevant prognostic biomarkers for pancreatic cancer patients, with MSI-H patients displaying a younger age and distinct tumor features.

Gene Ontology analysis indicated that SCLC-BM and LCLC-BM were associated with deregulated glial proliferation processes. These findings provide a comprehensive genomic characterization of BM from various lung cancer histologies.

These findings confirm the lower concordance between MMR-IHC and MSI-NGS in endometrial cancer compared with colorectal cancer when broad panels are used, underscoring the importance of tumor-specific interpretation even within tumor-agnostic assays. Although cut-off optimization improved agreement, the evidence remains insufficient for clinical implementation, and further validation studies are needed.

Data are available via ProteomeXchange with identifier PXD073693. This is the first study of the global proteomic differences between Lynch Syndrome and other forms of colorectal cancer.

This drop in sensitivity was attributed to the models' reluctance to confirm true protein loss, often categorizing the result as "Indeterminate" or "Inadequate". Crucially, the diagnostic certainty of the AI models increased dramatically only when a clear Internal Positive Control (IPC) was visible in the image, establishing the IPC as an indispensable feature for robust dMMR identification and differentiating true biological loss from technical artifacts.

Despite advancements in H. pylori research and technology over 20 years, no improvement was observed in H. pylori-positive tumor rates or early gastric cancer detection in Western Poland. Although molecular characteristics remained largely unchanged, the increased proliferation index in recently diagnosed cancers merits further study.

Immunohistochemistry revealed a loss of PMS2 expression, supporting a defect in MMR. This report documents an exceptional coexistence of malignant pleural mesothelioma and LS, suggesting that impaired DNA repair may lower the carcinogenic threshold for asbestos exposure. Clinicians should consider LS in patients with multiple or atypical malignancies, including mesothelioma, and recommend comprehensive MMR testing and genetic counseling for at-risk relatives.

Genotype-specific precision management optimizes the benefit-burden balance, enhances early cancer detection, reduces overtreatment, and enables personalized genetic counseling, advancing precision healthcare for LS families and addressing critical gaps in hereditary cancer care.

LS prevalence among patients with UTUC is similar to that among patients with colorectal and endometrial cancers, which provides a strong rationale for LS testing in this population. Further research is necessary to determine the optimal diagnostic strategy.

This case demonstrates that synchronous lung cancers may result from the combined effects of carcinogen-induced field cancerization and DNA repair deficiencies. The identification of PMS2 and ERCC2 alterations provides mechanistic evidence of genetic vulnerability, highlighting the importance of counseling, surveillance, and potential DNA repair-targeted strategies.