PMS2 (PMS1 protein homolog 2)

DMMR occurs in a minority of ACC, often without MSI. Although Lynch syndrome accounts for a subset of cases, dMMR is not predictive of clinical features or ICI response. Nonetheless, MMR testing remains important for identifying individuals at hereditary cancer risk.

Collectively, a TP53 abnormality at copy number (12/26, all cnLOH), sequence (55/60) and protein expression (46/48) level was detected in all 60 cases. In conclusion, integrated high-resolution copy number and histomolecular analysis expanded the spectrum of genetic changes associated with DHG-H3 G34, including the presence of universal TP53 abnormalities with frequent cnLOH-a copy number abnormality that has been largely unrecognized-for this new 2021 World Health Organization central nervous system tumor type.

Testing asymptomatic relatives identified two first-degree relatives with MSH2 mutations. These findings underscore the critical need for CRC-adapted preventive oncology and support the implementation of a national LS screening program in Greece, aligned with international guidelines.

She started combination therapy with ipilimumab and nivolumab, achieving complete metabolic and imaging response as confirmed by PET-CT at 12 months...She started treatment with pembrolizumab, achieving a sustained complete response at 12 months...Both cases illustrate the remarkable clinical benefit of immunotherapy in patients with early peritoneal recurrence of MSI-H/dMMR colon cancer, which is usually associated with poor prognosis. These cases highlight the need to consider the molecular profile in therapeutic planning and reinforce the emerging value of immunotherapy as a cornerstone in the management of these cases.

This case highlights that lung adenocarcinoma can be a manifestation of LS and underscores the critical importance of retrospective MMR testing in establishing the diagnosis. Furthermore, it demonstrates the efficacy of immune checkpoint inhibitions in advanced dMMR tumors.

An exploratory approach consisting of unmasking the results of the NGS analysis of 123 « research » genes involved in the carcinogenesis was applied to the 447 patients tested negative for the different genes of our diagnostic panel. This approach failed to identify other susceptibility genes to pancreatic adenocarcinoma.

This copula-based meta-analysis identifies gene-specific risks of endometrial and ovarian cancer in female Lynch syndrome carriers, supporting personalized gynecologic surveillance. It also notes higher breast cancer risks in MSH6 and PMS2 carriers, but conflicting evidence from large perspective databases prevents definitive conclusions about breast cancer as part of the Lynch syndrome spectrum.

Although dMMR was associated with initial treatment resistance, its unique immunogenicity was found to influence disease progression and subsequent treatment options. These findings suggested that MMR testing in LA-HNSCC patients had significant clinical value, not only aiding in the identification of patients who might benefit from subsequent immunotherapy but also potentially informing initial treatment strategies, such as the prospective exploration of combined immunotherapy approaches.

This study is limited due to a small cohort and limited available clinical data. Larger cohort studies and prospective clinical trials are necessary to validate and explore the interplay between molecular and immune biomarkers as well as general biological mechanism in paving therapeutic way in melanoma.

MLH1 loss identifies a subset of MMRd ECs with worse outcomes and lower CD8+ densities supporting substratification of this molecular subtype. Grade, histotype, ER, PR, L1CAM, CTNNB1 and p53 status do not add prognostic refinement within MMRd EC.

Genomic classifier tools help identifying aggressiveness of cancers and aid in personalized treatment decision-making. Joint efforts of multidisciplinary physicians are crucial to improve health outcomes for patients with PCa across the spectrum of this disease.

These findings suggest that current surveillance recommendations for individuals with LS should be re-evaluated. Lynch-Polyposis.