MSH2 (MutS Homolog 2)

P2, N=2, Active, not recruiting, National Cancer Institute (NCI) | N=240 --> 2 | Trial completion date: Oct 2027 --> Jun 2027 | Trial primary completion date: Oct 2027 --> Jan 2026

The findings favored metastatic colorectal carcinoma involving the pancreas in the setting of clinically suspected Lynch syndrome. This case emphasizes the importance of clinicopathologic correlation, cautious interpretation of MMR deficiency, and long-term multidisciplinary surveillance.

Metabolic pathway analysis also showed significant differences, with FMD preventing the upregulation of pathways involved in amino acid and nucleotide synthesis, potentially promoting tumour growth. Overall, the findings suggest that periodic FMD may result useful in a multimodal approach for LS management, counteracting gut microbiota alterations.

In this retrospective cross-sectional study, cascade testing was underused, especially among specific demographic groups, with clinical and cultural factors appearing to play a larger role than financial barriers. These findings may guide efforts to address barriers preventing wider uptake of cascade testing and improve cancer prevention efforts, particularly among racial and ethnic minority groups.

Understanding its histological features and immunohistochemical profile facilitates its diagnosis and differential diagnosis, including CK20 positivity and Ki-67 negativity in the superficial layer, and high Ki-67 expression with negative CK20 staining in the deep layer. KRAS gene mutation is also an important diagnostic feature.

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.

This enabled the decision to treat with immunotherapy for recurrence and also conduct family screening. In spite of the absence of colonic tumours, Lynch syndrome should be suspected in young patients with multiple tumours, particularly when supported by a relevant family history.

P2, N=76, Recruiting, Dechang Diao

Here we review and update on multiple aspects of LS in the context of CRC, including its genetic and molecular basis, current guidelines for molecular screening and variant classification. Furthermore, we review functional assays that have been used to determine the biological impact of genetic variants of uncertain significance (VUS) and discuss future perspectives in the field.

The patient received chemotherapy combined with radiotherapy and remained in stable clinical condition. Cytopathology offers a valuable diagnostic approach for patients with primary cardiac tumors in whom histological sampling cannot be obtained, and molecular testing using CB specimens can provide additional insights into the genetic profile of such rare tumors.

Here, we report a patient with locally advanced Gleason 5 + 5 = 10 prostatic adenocarcinoma harboring MSH2 and MSH6 genomic deletions with ultrahigh TMB (>250 mutations/megabase) in whom pembrolizumab resulted in a striking complete radiographic, pathologic, and molecular response...Similar T cells are also present in diverse cancers and expand exclusively in ICI-responsive patients. These findings inform on the cellular mechanisms by which immunotherapies may mediate profound responses in patients with dMMR solid tumors.

P3, N=170, Active, not recruiting, Sir Run Run Shaw Hospital | Recruiting --> Active, not recruiting | Trial completion date: Aug 2026 --> Dec 2028