MLH1 Clone 'SP56 antibody Host Rabbit
- Known as:
- MLH1 Clone 'SP56 (anti-) Host Rabbit
- Catalog number:
- 'AM11172PU-M
- Product Quantity:
- 0.5 ml
- Category:
- -
- Supplier:
- ACR
- Gene target:
- MLH1 Clone 'SP56 antibody Host Rabbit
Related genes to: MLH1 Clone 'SP56 antibody Host Rabbit
- Gene:
- MLH1 NIH gene
- Name:
- mutL homolog 1
- Previous symbol:
- COCA2
- Synonyms:
- HNPCC, FCC2, HNPCC2
- Chromosome:
- 3p22.2
- Locus Type:
- gene with protein product
- Date approved:
- 1993-11-24
- Date modifiied:
- 2019-04-23
- Gene:
- SELENBP1 NIH gene
- Name:
- selenium binding protein 1
- Previous symbol:
- -
- Synonyms:
- hSP56, hSBP, LPSB
- Chromosome:
- 1q21.3
- Locus Type:
- gene with protein product
- Date approved:
- 1999-01-15
- Date modifiied:
- 2018-07-27
Related products to: MLH1 Clone 'SP56 antibody Host Rabbit
Related articles to: MLH1 Clone 'SP56 antibody Host Rabbit
- Endometrial carcinoma is the most common malignancy of the female genital tract, and endometrial intraepithelial neoplasia (EIN, also termed atypical endometrial hyperplasia) is its recognized precursor lesion. Mismatch repair (MMR) deficiency, identified through loss of MLH1, PMS2, MSH2, and MSH6 expression on immunohistochemistry (IHC), is an important molecular event in endometrial carcinogenesis with diagnostic, prognostic, and hereditary (Lynch syndrome) implications. Comparatively few studies have examined the frequency of MMR loss in EIN. This study evaluated the proportion and patterns of MMR protein loss in EIN and endometrial carcinoma, with descriptive assessment of MMR protein loss according to histopathological grade of endometrial carcinoma. - Source: PubMed
Publication date: 2026/08/25
Maheshwari UjwalaAnand RamanaShah Vrutika - : This study aimed to investigate the relationships among mismatch repair (MMR) protein status, clinicopathological characteristics, and Programmed Death-Ligand 1 (PD-L1) expression in endometrial cancer, focusing specifically on heterogeneity within MMR-deficient (MMRd) tumors defined by distinct protein loss patterns. : This retrospective study enrolled 675 patients with surgically confirmed endometrial cancer at a tertiary medical group between January 2017 and June 2025. Patients were stratified according to specific MMR protein loss patterns. Clinicopathological parameters, the International Federation of Gynecology and Obstetrics (FIGO) stage, and PD-L1 combined positive score were compared across groups. : The cohort comprised 502 MMR-proficient (MMRp) and 173 MMR-deficient (MMRd) patients. Based on their specific MMR protein loss patterns, the MMRd cases were further stratified into three subgroups: MutLαcomplex loss (MLH1 ± PMS2, = 105), MutSαcomplex loss (MSH2 ± MSH6, = 60), and combined MutSα/MutLαcomplex loss ( = 8). Compared with MMRp tumors, MMRd tumors exhibited significantly lower BMI, higher tumor grade, more frequent lymphovascular space invasion, and elevated PD-L1 expression. Moreover, the 2023 FIGO staging system demonstrated superior performance in capturing the locally aggressive features of MMRd tumors relative to the 2009 edition. Within the MMRd cohort, the overall difference in combined positive score reached nominal significance ( = 0.049) but did not survive FDR correction (q = 0.290). Nevertheless, at the 1% and 5% cutoffs, MutLα-deficient tumors consistently showed higher PD-L1 positivity than MutSα-deficient tumors, with both associations remaining significant after FDR adjustment (q = 0.046 for both). Further subgroup analysis within the MutLα loss pathway revealed that isolated MLH1 loss was associated with a lower rate of CPS ≥ 1% (85.7%) compared with isolated PMS2 loss (91.3%) and combined MLH1/PMS2 loss (89.3%), in contrast. No significant heterogeneity in PD-L1 expression was observed across the MutSα-deficient subgroups. : MMRd endometrial cancer heterogeneity is primarily driven by MutSα and MutLα deficiency. MutSα loss associates with higher PD-L1 expression, suggesting a favorable immune profile warranting further study. Isolated MLH1 loss correlates with the lowest PD-L1 and aggressive features. These findings refine biological understanding and provide a hypothesis-generating rationale for biomarker-guided stratification in immunotherapy. - Source: PubMed
Publication date: 2026/09/11
Xiao YunyunYu HaoHuang DanyuLiu ShijiaWang YapingRen RanHu HanfuWang ShuoyanYu HaoyuLi YiHan Lu - Lynch syndrome (LS) is associated with gastric cancer (GC) and duodenal cancer (DC), but risk estimates and the role of upper endoscopy surveillance remain uncertain. - Source: PubMed
Publication date: 2026/09/25
Ausina-Poüs VíctorBaile-Maxía SandraSáez-Rico MaríaSala-Miquel NoeliaMangas-Sanjuan CarolinaMartínez-Tévar IreneSánchez-Ardila CarmenZapater PedroCavestro Giulia-MartinaMannucci AlessandroLevi ZoharIdos GregoryBurke Carol AJover Rodrigo - Cancer susceptibility testing is rapidly advancing beyond specialist genetics clinics into routine oncology and population-level genomics initiatives. This expansion positions germline pathogenic variants in cancer susceptibility genes and polygenic risk scores as crucial tools for precision prevention, surveillance, and early detection. However, implementation has outpaced the evidence needed to justify testing at scale, particularly in well populations. For a small number of first-wave genes-including BRCA1, BRCA2, MLH1, and MSH2-cancer risks are well established and downstream medical interventions are supported by substantial observational evidence, albeit with an absence of randomised trials. Contrastingly, for many later discovered genes now included on multigene panels, penetrance estimates remain uncertain, variant-specific risks are poorly resolved, and evidence is scarce or absent regarding mortality reduction, quality of life benefit, or cost-effectiveness for the recommended downstream interventions. Polygenic risk scores offer promise for stratified prevention, but their discriminatory capacity is constrained, performance is ancestry dependent, and clinical utility remains uncertain in most settings. Building on the Lancet Oncology Commission on cancer genomics and precision oncology, this Policy Review examines the evidentiary, clinical, and health-system challenges associated with cancer susceptibility testing across clinical care and public health prevention. We argue that the value of such testing should be assessed in terms of its clinical value and public health utility, with careful attention to the context in which testing is offered. We propose a tiered, context-specific approach to implementation, aimed at distinguishing settings in which susceptibility testing could provide a net benefit from those scenarios in which its use should remain restricted, highly selective, or confined to research. - Source: PubMed
Publication date: 2026/09/25
Turnbull ClarePerdomo SandraDomchek SusanFoulkes William DPharoah PaulAshton-Prolla PatriciaSirohi BhawnaMateo JoaquinRobbins Hilary ASullivan RichardLawler MarkCasolino Raffaella - GHKL ATPases share a unique Bergerat ATP-binding fold and regulate diverse biological processes through ATP-dependent conformational changes. An early step of ATP hydrolysis in this family has been attributed to a single highly conserved glutamate residue proposed to function as the general base. However, mutations of this residue impair both the ATPase activity and ATP binding, complicating interpretation of its catalytic role. Re-examination of the high-resolution crystal structures revealed a second conserved acidic residue positioned within a hydrogen-bonding distance from the nucleophilic water molecule. Using MutL and GyrB as model enzymes, we combined systematic mutagenesis, ATPase and ATP-binding assays, and X-ray crystallography to dissect the roles of these residues. We show that alignment of the nucleophilic water can be maintained as long as the conserved glutamate retains hydrogen-bonding capability, whereas efficient ATP hydrolysis requires proton-accepting capacity at least in one of the two acidic residues. These results indicate that the conserved glutamate primarily governs positioning of the nucleophilic water, while activation of this water for catalysis is achieved through cooperative general base function of the two acidic residues. Extending this framework to human MutL homologs, PMS2 and MLH1, we showed that clinically reported variants of uncertain significance in these DNA mismatch repair proteins substantially reduced the ATPase activity, indicating functional impairment. Together, our findings refine the catalytic mechanism of GHKL ATPases and provide a structural and functional framework for interpreting disease-associated variants in GHKL ATPases. Phylogenetic and ancestral state analysis further indicated that the second acidic residue was likely to be present in the common ancestor of major GHKL ATPase lineages but was later modified in a branch, including Hsp90, suggesting evolutionary remodeling of the catalytic mechanism in the branch. - Source: PubMed
Publication date: 2026/09/25
Fukui KenjiShibuya AyakaMurakawa TakeshiYano Takato