PMS2 (PMS1 protein homolog 2)

However, many patients with these variants have urothelial cancer of the bladder only. Broader genetic testing, particularly in those with a suggestive personal or family cancer history, may help identify patients at risk who might otherwise be missed.

and be estrogen receptor positive [p < 0.001] progesterone status positive [p < 0.001] and HER2 negative [p = 0.043]...This can help clinicians adapt when counseling these patients. Furthermore, ILC keeps its distinctive characteristics independent of the genetic backdrop.

MLH1 loss was closely linked to early-onset CRC and may point to a hereditary risk. Regular testing for MMR proteins can help with diagnosis, screening for Lynch syndrome, and choosing the best treatment.

The c.579delG variation in the MSH2 protein led to truncation from 934 amino acids to 212 amino acids, altered the sequence of the Domain 2 region, and caused the loss of Domains 3, 4, and 5. The two missense variants of the PMS2 gene (PMS2:NM_000535:exon11:c.1847T>C:p.V616A and PMS2:NM_000535:exon14:c.2444C>T:p.S815L) were considered variants of uncertain significance, whereas the novel frameshift variant of the MSH2 gene (MSH2:NM_000251:exon3:c.579delG:p.Q193fs) was considered likely pathogenic.

This case underscores the importance of early response evaluation in ICI-treated MSI-H tumors. Rapid disease progression requires prompt differentiation between HPD and pseudoprogression, emphasizing the necessity of timely therapeutic modification.

In this prospective Japanese cohort, approximately one in four patients with EC had dMMR, with clinicopathologic features skewing toward a higher grade. Notably, many dMMR tumors were grade 2-3, suggesting that a substantial proportion of patients may fall outside the conventional criteria for fertility-sparing treatment.

FOLR1 expression in the two cases was weak and below currently used clinical cutoffs for mirvetuximab soravtansine eligibility...Only a subset of anaplastic carcinomas of the ovary express targetable tumor antigens at low levels, suggesting that these may have limited benefit from antibody-drug conjugates. Likewise, due to mismatch repair proficiency and low tumor mutational burden, immunotherapy is unlikely to be effective in this rare disease.

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.