PMS2 (PMS1 protein homolog 2)

These findings support the value of routine IHC-based MMR testing in CRC patients. However, confirmatory molecular testing (e.g., MSI analysis, BRAF V600E mutation, MLH1 promoter methylation, or germline sequencing) is necessary to differentiate sporadic from Lynch syndrome-associated dMMR cases and to fully guide Lynch syndrome screening and immunotherapy decisions.

MSI testing by MSI PCR, however, showed a microsatellite stable result. This highlights how MSI PCR may not be sufficiently sensitive in detecting MSI-H status in tumour types outside of colorectal carcinomas.

The worse outcomes of rectal MAC appear to be driven largely by late-stage presentation, possibly owing to later diagnosis. MAC nonetheless carries a distinct immune phenotype, detectable even in histologically normal surrounding mucosa, that likely contributes to its treatment resistance. These observations provide a basis for developing histotype-specific approaches to both early detection and treatment in this uncommon but clinically challenging tumour subtype.

Our ML approach accurately predicted MSI status in colorectal and uterine cancers using multiomics data derived from NGS, without relying on direct microsatellite sequencing. The ability to identify MSI-high tumors among indeterminate cases demonstrates potential to improve diagnostic precision and ensures timely access to immunotherapy for patients with MSI-high disease.

We report an extremely rare case of SR of poorly differentiated CRC with dMMR and marked TILs. Enhanced tumor immunogenicity associated with dMMR and immune activation may contribute to CRC regression.

Median overall survival was 23 months, reflecting the high mortality burden of mCRC after hepatectomy. Among all molecular markers evaluated, pS6 was the only one independently associated with worse disease-free survival and higher mortality risk, consistent with its role as a surrogate marker of PI3K/AKT/mTORC1 pathway activation, though a direct causal relationship cannot be established from the present data. A significant association between pS6 and FUS positivity suggests a possible convergence of oncogenic pathways warranting further investigation. Postoperative complications were independent predictors of recurrence, and adjuvant chemotherapy was the strongest independent predictor of improved overall survival. Given the retrospective single-center design and limited sample size, these findings are hypothesis-generating and require prospective multicenter validation before clinical application.

Overall, 18.6% of women with young breast cancer had PVs in 18 genes tested, including 6.8% in a gene other than BRCA1 or BRCA2. Study results suggest that genetic testing should be offered to all women diagnosed breast cancer at the age of 40 or younger.

P=N/A, N=150, Recruiting, Centre Hospitalier Universitaire de Nīmes | Not yet recruiting --> Recruiting | Initiation date: Dec 2025 --> Mar 2026

Microsatellite instability high status (30.77%) and Lynch syndrome (3.85%) can occur in patients with only nonclassic loss of MMR proteins (without the B pattern). It is necessary to deepen our understanding of nonclassical MMR expression patterns to avoid missing patients with microsatellite instability high status and Lynch syndrome.

These findings raise suspicion for Lynch syndrome. This case is interesting because seminoma and colorectal cancer were both identified in a patient with features suggestive of a hereditary cancer syndrome.

This case highlights the use of immunotherapy and screening for pediatric CMMRD-associated colorectal adenocarcinoma in the setting of a novel PMS2 variant.

These pilot study results suggest that conventional histopathology can be a cost-effective screening tool for identifying endometrial endometrioid cancers likely to be MMR-deficient. Larger cohorts are needed to further validate the findings.