MSH6 expression

P2, N=240, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

Microsatellite instability in oropharyngeal SCC is demonstrated by the association between loss of protein expression and its heterodimer imbalance with disease-free survival. It was demonstrated that the imbalance of the MMR complex can consequently lead to resistance to treatment and a decrease in disease-free survival in p16 + oropharyngeal SCC tumors.

More studies are needed to further define the role of MSI in melanoma prognosis and response to immunotherapy.

In conclusion, we report recurrent fusions of the GRHL genes in a distinctive subset of sebaceomas harbouring infundibulocystic differentiation, a frequent organoid growth pattern and lack of mismatch repair deficiency.

PT is associated with a reduction in MMR expression, notably for the MSH2 protein, while it does not appear to influence HER2 expression.

P2, N=130, Not yet recruiting, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Union Hospital, Tongji Medical College, Huazhong University of

P2, N=18, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Aug 2028 --> May 2027 | Trial primary completion date: Aug 2025 --> Jun 2024

The expressions of MSH2, MSH6, and villin are closely correlated with the pathological features of colon cancer patients. Evaluating the expression of the three proteins may assist in the clinical diagnosis, treatment, and prognosis evaluation of colon cancer.

This is a unique case of a patient who carries two pathogenic variants in genes associated with LS (MSH6 and MSH3), who developed metastatic recurrent rectal adenocarcinoma, as well as synchronously diagnosed stage 2 TNBC, with a complete clinical response in breast cancer to pembrolizumab. This case highlights the significant relationship between TMB and its utility as a predictive indicator of response to immunotherapy. It confirms prior studies suggesting that it is a promising biomarker, with the limitation that high TMB is rare in TNBC.

This study provides evidence that the MSH2 nonsense mutation c.354T>A is a highly likely pathogenic mutation and is responsible for typical LS-associated endometrial carcinoma. It emphasizes the importance of genetic counseling for proband family members to facilitate early diagnosis of LS-related carcinoma.

Salivary glands' ACC shows imbalance of the MMR complex and loss of expression of its components is associated with the overall survival of these patients.

Fn treatment accelerated the malignant progression of CRC in mice, and this process is inhibited by miRNA-155-5p antagomir. Fn in CRC upregulated miRNA-155-5p by activating TLR4/NF-κB signaling to inhibit MSH6, and this regulatory pathway may affect MSS of cancer cells.

Heterogenous mismatch repair protein staining in colorectal cancer exhibits distinct associations with tumor location, stage, microsatellite instability, BRAF mutation and prognosis. It is recommended to report MSH6 heterogeneity as it may indicate microsatellite instability-high. See Video Abstract.

These findings suggest the need for enhanced screening, early detection, and tailored treatment approaches in Bahrain. Further research and robust national cancer registries are warranted to fully understand the underlying risk factors and guide evidence-based interventions to mitigate the burden of this disease.

Assessing TB in surgical specimens can provide information about the response to treatments, such as immunotherapy, which have been introduced into the treatment of GC in recent years. In this study, we demonstrated the relationship between TB, PD-L1 and MSI status in GC: Low grade TB, assessed by methods H.Ueno and L.Wang, correlates with MSI-positive status, but not with PD-L1-status of GC.

Furthermore, most of the HPV-associated SCCs were MMR stable. This study found no significant association between MMR status and PD-L1 expression in cervical SCCs.

In conclusion, our study provides valuable insights into the expression of mismatch repair in colorectal adenocarcinoma through immunohistochemistry analysis conducted at our tertiary care centre. These findings hold significant clinical implications, suggesting further testing for BRAF and MLH1 Promoter Hypermethylation to confirm possibility of Lynch syndrome.

P3, N=700, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Apr 2024 --> Apr 2025 | Trial primary completion date: Apr 2024 --> Apr 2025

Geographical and ethnic factors might influence peculiarities in MMR protein loss. Our findings also highlight new gene expression networks and crucial regulatory molecules in CRC metastasis, enhancing our comprehension of the mechanisms driving distant metastasis.

P3, N=400, Recruiting, Massachusetts General Hospital | Trial completion date: Apr 2026 --> Dec 2027 | Trial primary completion date: Apr 2025 --> Dec 2026

P2, N=44, Completed, University of California, San Francisco | Active, not recruiting --> Completed | Trial completion date: Nov 2025 --> Jan 2024 | Trial primary completion date: Nov 2025 --> Jan 2024

The findings suggest a potential correlation between the abundance of B. fragilis and alterations in the expression of MMR genes. Since these genes can play a role in modifying colon cancer, investigating microbial characteristics and gene expression changes in CRC could offer a viable solution for CRC diagnosis.

Reduced MSH6 expression could serve as a potential biomarker for predicting better prognosis, active immune status, higher immune checkpoint expression level and better responsiveness to ICIs treatment in EC. MSH6 may become a potential target for treating solid tumors.

P2, N=240, Recruiting, National Cancer Institute (NCI) | Initiation date: Jun 2024 --> Dec 2023

P2, N=21, Recruiting, University of Texas Southwestern Medical Center | Not yet recruiting --> Recruiting

Modified FOLFOX6(mFOLFOX6)regimen was given as a first line chemotherapy and was followed by pembrolizumab after 1 cycle of the mFOLFOX6, because microsatellite instability(MSI)test of the tumor showed high-frequency MSI...Genetic test identified a MSH2 pathogenic variant leading to the diagnosis of Lynch syndrome. The present case shows the importance of MSI test or IHC-MMR before the treatment of metastatic colorectal cancer.

This study revealed that high expression of MMR proteins is a common feature of DLBCL associated with lower tumor-infiltrating T cells, MYC and p53 overexpression, and context-dependent prognostic effects. In contrast, dMMR and loss of MMR proteins are infrequent and have no significant prognostic effects in DLBCL treated with standard chemoimmunotherapy. These results may have implications for understanding DLBCL biology and the low efficacy of PD-1 blockade immunotherapy in DLBCL.

This case highlights the complexities of understanding genetic susceptibility in childhood cancers. We propose a multifactorial oligogenic inheritance of cancer susceptibility in this patient through several mechanisms of genomic instability.

P2, N=21, Not yet recruiting, University of Texas Southwestern Medical Center | Trial completion date: Oct 2026 --> Oct 2028 | Initiation date: Oct 2023 --> Jan 2024 | Trial primary completion date: Oct 2025 --> Oct 2026

Secondary rectal cancer with endometrial origination in the absence of endometriosis and serosal implants was extremely rare. Therefore, we should pay more attention to this rare but possible presentation for appropriate diagnosis and treatment of these patients.

P2, N=35, Recruiting, Dana-Farber Cancer Institute | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Oct 2023 --> Oct 2024

Functional investigation of this inversion in a laboratory setting revealed a resultant abnormal protein function. Thus, we have identified an unusual, small germline inversion in a mismatch repair gene that does not lead to a premature stop codon yet appears likely to be causal for the observed cancers.

PD-1/PD-L1 expression may contribute to the progression and poor prognosis of bladder cancer. However, further studies are required to research the clinical utility.

Analysis of clinical samples showed that USP7 expression was significantly higher in hypertrophic scars (0.35±0.05), scar ulcers (0.43±0.04), and scar cancers (0.61±0.03) than in normal skin (0.18±0.04), P<0.05. USP7 may be a clinical biomarker for the progression of cicatricial ulcer cancer.

Of these patients, 14 (23.7%) had MMR deficiency. The MMR deficient group had a higher proportion of early stage (stage I and II) compared to the MMR proficient group (78.6% vs. 64.4%).

This study showed a high prevalence of dMMR in cholangiocarcinoma with dMMR being the independent prognostic factor for good survival, especially in early-stage CCA and for patients who received adjuvant chemotherapy. dMMR should be the marker for selecting patients to receive a specific adjuvant treatment after resection for CCA.

In this study, immunohistochemical screening of MMR proteins for Lynch syndrome was performed in a series of prostate cancer cases. The prevalence of Lynch syndrome in localized prostate cancer was 0.8%, which is low compared with other Lynch syndrome-associated cancers.

Our study establishes MSH6 or MSH2 as an oncogene that is prominently overexpressed during HCC progression which provides new targets for HCC with MVI.

P2, N=240, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | Initiation date: Sep 2023 --> Jun 2024

Interestingly, all 16 medullary carcinomas that were analyzed showed characteristics corresponding to the presence of both dMLH1 and BRAFV600E mutation (P = .01). These results suggest that colorectal medullary carcinomas can be diagnosed based on their unique characteristics of harboring the BRAFV600E mutation and exhibiting dMLH1 expression.

MTS is a unique condition that necessitates continuous surveillance. When sebaceous adenoma arises in atypical regions, it is important to consider additional screening to eliminate the likelihood of MTS. Poster type: Poster Defense