PMS2 (PMS1 protein homolog 2)

DOG1-positive CAFs were associated with better overall survival. This study suggests that DOG1 expression is detected in a high proportion of CRC because it is expressed in neoplastic cells of various histological subtypes of CRC that secrete gel-forming mucins, independently of mucinous features or in CAFs of conventional adenocarcinomas.

He subsequently received ramucirumab-based therapy, paclitaxel, and irinotecan...Pembrolizumab combined with capecitabine and oxaliplatin (CAPOX) was initiated as fifth-line therapy, resulting in notable regression of hepatic and nodal metastases. This case underscores the clinical importance of early MSI/MMR and genomic testing and suggests that re-administration of ICI plus chemotherapy may be a therapeutic option for selected patients with advanced gastric cancer who initially show limited response to ICI-based therapy.

Our findings expand the spectrum of known APC variants and provide functional evidence for the pathogenicity of this variant. The rare co-occurrence of FAP and MSI-H in the proband enriches the molecular phenotypic spectrum of FAP-related tumors.

Our hypothesis-generating findings suggest that dMMR/MSI-H may serve as a biomarker of sensitivity to single-agent ICIs in advanced UTUC. External validation in larger, ideally prospective, studies is needed to confirm the effectiveness and durability of immune checkpoint blockade in this molecular subgroup.

Combined loss of MSH6 and PMS2 (MSI-H) was found in 30% of cases, particularly in poorly differentiated tumors, T3 stage tumors, stage II and III cancers, and node-positive groups. Thus, understanding of microsatellite instability (MSI) detection in colorectal carcinomas (CRCs) using immune histochemical markers MSH6 and PMS2, improving diagnostic and prognostic approaches for CRC.

A composite score integrating p53 binary status (aberrant vs. wild) with Wnt3 and whole β-CTN indices predicted survival beyond stage; each 1-point increase conferred a 2.56- and 1.77-fold higher risk of cancer-specific and overall mortality (p = 0.004 and 0.04). These findings suggest that p53 dysfunction is associated with alterations in Wnt/β-CTN signaling and that integrating signaling markers with staging may improve prognostic assessment in colorectal cancer.

Notably, the presence of MMRd subtype in such synchronous tumors does not inherently indicate Lynch syndrome. This case underscores the importance of integrating molecular testing and clinical manifestations to accurately diagnose multiple primary malignancies and formulate tailored treatment plans.

This case illustrates the characteristic clinicopathological and molecular features of CMMRD-associated pediatric high-grade glioma and underscores the critical role of routine mismatch repair immunohistochemistry. Integrated histological and genomic evaluation is essential for accurate diagnosis, appropriate genetic counseling, and potential therapeutic implications. Key Points • This case represents a pediatric high-grade glioma arising in the setting of PMS2-related constitutional mismatch repair deficiency (CMMRD). • The tumor exhibited an ultra-hypermutated profile with co-occurring TP53, PIK3CA, PIK3R1, and PTEN mutations. • Loss of PMS2 expression in both tumor and non-neoplastic cells was critical in establishing the diagnosis of CMMRD. • The presence of a developmental venous anomaly may relate to underlying PIK3R1 pathway alterations. • Routine mismatch repair immunohistochemistry is essential in pediatric high-grade gliomas, even in the absence of a family history.

Genetics has been shown to affect several aspects of disease, including carcinogenesis, onset age, clinicopathological features, prognosis, and therapy response. In this review, we will investigate the impact of germline PVs in different genes on genetic susceptibility to the development of inherited EC, discussing the potential cancer risk in mutation carriers as well as prognostic implications and current therapeutic approaches, also evaluating the possibility of carrying out a more extensive routine genetic analysis for EC women, in order to increase the diagnostic power, improve prevention and surveillance strategies in genetically predisposed subjects, and implement tailored therapies.

dMMR status, especially dMutL, might be associated with clinicopathologic characteristics, which might support decision-making in clinical practice. These findings require validation in larger cohorts but may inform clinical screening practices in resource-limited settings.

In this Portuguese cohort, nearly 12% of consecutive real-world MGPT-tested gastric cancer patients had germline pathogenic or likely pathogenic variants, predominantly in mismatch repair genes but also in CHEK2 and BLM. These findings further illustrate the heterogeneity of hereditary gastric cancer beyond classical CDH1 mutations and support the integration of MGPT into clinical care to identify at-risk individuals not captured by current criteria. Larger multicentre studies are warranted to validate these results and clarify the role of emerging susceptibility genes.

However, differences in TIL rate and CD45RO expression indicate that each of the SGT tumor types may have distinguished immune microenvironments. Malignant SGTs have higher infiltration of activated immune cells, and, thereby, these cells can be considered as good indicators of patient's status.