Altogether, we show that NRF2 protein levels are increased in MSH2-deficiency and associated neoplasia, but loss of NRF2 attenuates tumorigenesis. Activation of NRF2 may not be a feasible strategy for chemoprevention in LS.

7 months ago

Preclinical • Journal

MSH2 (MutS Homolog 2) • NQO1 (NAD(P)H dehydrogenase, quinone 1)

MSH2 deletion

over1year

Exploring the Expression and Prognosis of Mismatch Repair Proteins and PD-L1 in Colorectal Cancer in a Chinese Cohort. (PubMed, Cancer Manag Res)

Deletion of MMR proteins and expression of PD-L1 are closely related to clinicopathological characteristics and overall prognosis of CRC patients. This suggests the relevance of MMR and PD-L1 as potential biomarkers for treatment of CRC patients.

over 1 year ago

Journal • Mismatch repair • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)

PD-L1 expression • MSI-H/dMMR • MSH2 deletion • MLH1 deletion • MSH6 deletion • MSH6 expression

over1year

Time course genomic characterization reveals progressive accumulation of mutations during tumor development in a Lynch syndrome mouse model (AACR 2023)

Our preliminary data indicates that combined fecal FSM status and MSI score can be potentially used as a biomarker to monitor the tumor development and disease progression for LS colorectal cancer.Funded by the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261201500003I

over 1 year ago

Preclinical • MSi-H Biomarker

TP53 (Tumor protein P53) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • PMS2 (PMS1 protein homolog 2) • EPCAM (Epithelial cell adhesion molecule)

TP53 mutation • MSI-H/dMMR • MSH2 deletion

over2years

Lynch Syndrome-Associated Endometrial Cancer With Combined EPCAM-MSH2 Deletion: A Case Report. (PubMed, Front Oncol)

The patient underwent interstitial brachytherapy (BT) of the presacral metastatic lymph node. This case highlights that patients with LS-EC who are carriers of combined EPCAM-MSH2 deletion might experience better oncologic outcomes even with early recurrence.

over 2 years ago

Review • Journal

MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • EPCAM (Epithelial cell adhesion molecule)

MSH2 deletion

almost3years

GATA3 expression in Metastatic Prostatic Adenocarcinoma (USCAP 2022)

To our knowledge, this is the first study exploring GATA3 expression in mPCa. Although only 6% of our cases showed positive GATA3 staining, our findings provide evidence of aberrant GATA3 expression in mPCa. Pathologists should be aware of this potential diagnostic pitfall and use a panel-based approach in the distinction of urothelial vs.

almost 3 years ago

IO biomarker

TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSH2 (MutS Homolog 2) • GATA3 (GATA binding protein 3) • NKX3-1 (NK3 homeobox 1)

TP53 mutation • TMB-H • MSH2 deletion

over3years

Cytoplasmic MSH2 Related to Genomic Deletions in the MSH2/EPCAM Genes in Colorectal Cancer Patients With Suspected Lynch Syndrome. (PubMed, Front Oncol)

Our study also provides clinical evidence for the beneficial effect of the PD-1 inhibitor pembrolizumab for CRC patients that exhibit cytoplasmic MSH2 staining. Our study demonstrates that the rare cytoplasmic MSH2 staining pattern should be fully recognized by pathologists and geneticists. Given the specific genotype-phenotype correlation in LS screening, we advocate that all CRC patients with cytoplasmic MSH2 staining in histology should be screened for LGRs of EPCAM and MSH2.

over 3 years ago

Clinical • Journal • PD(L)-1 Biomarker • IO biomarker

MSI (Microsatellite instability) • MSH2 (MutS Homolog 2) • EPCAM (Epithelial cell adhesion molecule)

MSH2 mutation • MSH2 deletion

Keytruda (pembrolizumab)

over3years

[VIRTUAL] Germline mutations in MSH2 and ATM gene in patients with GIST (Gastrointestinal stromal tumor) and second epitelial tumors. (ASCO 2021)

Our analysis suggests that GIST diagnosis could be tumor-related to multiple hereditary tumor syndromes as Lynch Syndrome and Ataxia-Teleangectasia syndrome, the latter being linked in eterozygosis to tumor susceptibility to breast in female . This report represents a high value in terms of genetic counseling for relatives and in terms of therapeutic implications for the patients.

over 3 years ago

Clinical • BRCA Biomarker • MSi-H Biomarker

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • ATM (ATM serine/threonine kinase) • NF1 (Neurofibromin 1) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • BRCA (Breast cancer early onset) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • EPCAM (Epithelial cell adhesion molecule) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • AURKB (Aurora Kinase B) • MUTYH (MutY homolog) • XRCC2 (X-Ray Repair Cross Complementing 2) • CDK7 (Cyclin Dependent Kinase 7)

MSI-H/dMMR • ATM mutation • KIT mutation • MSH2 mutation • MSH2 deletion

over3years

A novel founder MSH2 deletion in Ethiopian Jews is mainly associated with early-onset colorectal cancer. (PubMed, Fam Cancer)

Carriers from the oldest generations were diagnosed after age 45 years (mean 57), and carriers from the younger generation were diagnosed before age 45 years (mean 30). Awareness of this founder deletion is important to improve patient diagnosis, institute surveillance from an early age, and refer patients for genetic counseling addressing the risk of bi-allelic constitutional MMR deficiency syndrome.

over 3 years ago

Journal

MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)

MSH2 deletion

over3years

Analysis of the Clinicopathological Characteristics of Stage I-III Colorectal Cancer Patients Deficient in Mismatch Repair Proteins. (PubMed, Onco Targets Ther)

Our results show that dMMR status may be more likely exist in female and younger (≤55 years) patients with a greater tumor burden (>5cm), right colon, T4 stage disease, poor differentiation and mucinous adenocarcinoma. Loss of PMS2 and MLH1 is the most common pattern of MMR protein expression deficiency, followed by concurrent deletion of MSH2 and MSH6.

over 3 years ago

Clinical • Journal • Mismatch repair

MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)

MSI-H/dMMR • MSH2 deletion • MLH1 deletion • MSH2 deletion + MSH6 deletion • MSH6 deletion

4years

Complete Loss of EPCAM Immunoexpression Identifies EPCAM Deletion Carriers in MSH2-Negative Colorectal Neoplasia. (PubMed, Cancers (Basel))

All lesions showing a lack of EPCAM expression belonged to patients with EPCAM 3'-end deletions. EPCAM IHC is a useful screening tool, with 100% specificity to identify LS patients due to EPCAM 3'-end deletions in MSH2-negative CRC and MSH2-negative colorectal polyps.

4 years ago

Journal

MSH2 (MutS Homolog 2) • EPCAM (Epithelial cell adhesion molecule)

MSH2 mutation • MSH2 deletion • EPCAM expression

over4years

Integrated immunohistochemical and molecular analysis improves diagnosis of high-grade carcinoma in the urinary bladder of patients with prior radiation therapy for prostate cancer. (PubMed, Mod Pathol)

Our findings highlight the importance of considering prostatic origin in high-grade carcinoma of the urinary bladder of patients with a history of treated prostate cancer, even when the immunohistochemical findings favor urothelial carcinoma. In a subset of cases, an approach that integrates immunophenotypic and molecular data may help correctly assign site of origin and prevent misdiagnosis that can result from overreliance on any individual immunohistochemical or molecular result.

over 4 years ago

Clinical • Journal

AR (Androgen receptor) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • ERG (ETS Transcription Factor ERG) • TMPRSS2 (Transmembrane serine protease 2) • KLK3 (Kallikrein-related peptidase 3)

MSH2 deletion • TMPRSS2-ERG fusion • MSH6 deletion