Ask about this productRelated genes to: MLH1 antibody
- 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
Related products to: MLH1 antibody
Related articles to: MLH1 antibody
- Mismatch repair-deficient (dMMR) sarcomas are rare and incompletely characterized. Here, we studied 39 sarcomas with high microsatellite instability (MSI-H) and/or biallelic MMR gene inactivation (21 MSH2, 9 MLH1, 4 PMS2, 4 MSH6, 1 EPCAM). All tumors evaluated with immunohistochemistry (IHC; n = 36) showed loss of MMR protein expression. Eight sarcomas were index neoplasms among the 15 patients with documented Lynch syndrome. Eighteen of 1531 sarcomas (1.2%) in our sequencing database were dMMR, with enrichment in pleomorphic rhabdomyosarcoma (PRMS; 1/5), uterine leiomyosarcoma (LMS; 7/124; 5.6%), and unclassified/undifferentiated pleomorphic sarcoma (UPS; 6/259; 2.3%). MMR IHC screening of independent cases confirmed MMR deficiency in PRMS (2/20), uterine LMS (2/20), and unclassified/UPS (1/20). Two histologic patterns were identified among unclassified/UPS. Ten tumors, designated "distinctive lobulated inflammatory sarcoma" (DLIS), showed lobular architecture, florid inflammation, and histiocytoid, variably pleomorphic neoplastic cells. All 6 patients with DLIS and follow-up (median: 6.0 y; range: 3 mo to 8.6 y) were alive with no evidence of disease (ANED), and 2 DLIS responded completely to immune checkpoint inhibition. A morphologically different group of 6 unclassified high-grade sarcomas showed sheets of epithelioid-to-rhabdoid cells with eosinophilic cytoplasm; among 5 patients with follow-up (median: 1.1 y; range: 4 mo to 6.9 y), only 1 was ANED. Surprisingly, all 3 PRMS patients with follow-up (median: 5.7 y; range: 4.2 to 8.3 y) were ANED, including 2 with complete responses of metastases to systemic therapy. We conclude that PRMS, uterine LMS, and unclassified/UPS showed sufficiently prevalent MMR deficiency to justify prospective MMR IHC screening for Lynch syndrome and to identify patients who might benefit from immune checkpoint inhibition. Histologic subtyping of unclassified sarcomas predicted prognosis and therapeutic response. We propose universal MMR IHC screening of (1) PRMS, (2) uterine LMS, (3) unclassified/UPS, and (4) any sarcoma in a patient with a personal or family history of Lynch syndrome. - Source: PubMed
Publication date: 2026/06/12
Odintsov IgorNowak Jonathan ABaranov EstherAlcindor ThierryHaddox Candace LVenkataraman VinayakSholl Lynette MGeorge SuzanneDoyle Leona ARedston MarkPapke David J - Caseinolytic peptidase P (ClpP) plays a key role in maintaining cellular homeostasis for mitochondrial quality control. However, the specific function of ClpP during meiosis and its subcellular localization in spermatocytes remain poorly understood. - Source: PubMed
Publication date: 2026/06/11
Feng Hai-WeiGao Yan-LinJiang Bin-JieZubair MuhammadLiu Dong-TengXu Zhi-ShenWang Zheng-ZhuWang Hong-LingWang Xue-MeiSun Jing-XiaZeng Guo-HuaHuo Li-Jun - Lynch syndrome is an autosomal dominant hereditary cancer syndrome caused by germline mutations in DNA mismatch repair genes. Currently, Lynch syndrome has well-established associations with colorectal and endometrial cancers. However, a definitive association between Lynch syndrome and pancreatic neuroendocrine tumors (P-NETs) remains unestablished. Herein, we report the case of a 38-year-old male with a maternal family history of Lynch syndrome who presented with hypoglycemia, abdominal pain, and diarrhea. Imaging revealed a 5.6 cm pancreatic tail mass with hepatic, lymph node, and osseous metastases. Synchronous sigmoid adenocarcinoma was identified during admission. Germline testing confirmed a pathogenic MLH1 mutation, and liver biopsy of the P-NET demonstrated loss of MLH1 and PMS2 expression. The patient was treated with capecitabine and temozolomide (CAPTEM) chemotherapy, pembrolizumab, long-acting repeatable octreotide (octreotide LAR), and diazoxide for hypoglycemia management. Disease progression with spinal epidural extension necessitated palliative radiation and intravenous immunoglobulin for severe thrombocytopenia. This case highlights the expanding phenotypic spectrum of Lynch syndrome and suggests that P-NETs may represent a rare but clinically significant manifestation. Early recognition of this association supports comprehensive genetic testing, enables the use of precision immunotherapy, and underscores the need for expanded surveillance strategies in patients with atypical tumor profiles. - Source: PubMed
Publication date: 2026/06/08
Mudupula Vemula Sai SushruthaSanka SoumithNatarajan VarunVarghese Merryl TIsaac Daniel - Lynch syndrome significantly increases the risk of developing colorectal cancer (CRC) due to an inherited defect in mismatch repair (MMR). Early detection relies on the identification of pathogenic mutations in patients with a family history of cancer, but few canonical Lynch mutations exist. Here, we describe four CRC patients found to carry an identical mutation in the MLH1 gene. Despite a strong family history of cancer, the MLH1 mutation was labeled discordantly regarding pathogenic potential. This highlights the need for improved diagnostics to screen for non-canonical Lynch variants. In addition to designing a novel digital PCR (dPCR) assay to rapidly detect MLH1 gene variants, we conducted in-depth analyses via molecular modeling, mutational signature analyses, and functional genetic assays to demonstrate that the MLH1 mutation results in a definitive MMR defect that increases cancer risk. This study emphasizes the need for improved diagnostic tools to identify pathogenic mutations in diverse populations. - Source: PubMed
Publication date: 2026/06/10
Moldenhauer Matthew RMahadevan AdityaHom CameronNguyen Angie T MRangel ValeriaHasson SophieHsu Ning-HsiangUbbaonu ChimezieNathan DeepikaChandan Vishal SShen Kaiyuan VDamozonio Ellianna MZhou Grace GChichili TanviLe AnMasri SelmaDayyani FarshidQiao FengValerin Jennifer BPannunzio Nicholas R - To analyze the occurrence and distribution of high-level microsatellite instability (MSI-H) in precancerous lesions and histological subtypes of endometrial cancer, to compare the concordance rate between mismatch repair protein deficiency (dMMR) and MSI-H, to investigate the incidence of minimal microsatellite shift in the development of endometrial cancer, and to explore potential solutions for accurate MSI-H diagnosis. A total of 848 endometrial lesion samples that underwent molecular typing at the Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University from January 2023 to January 2024 were collected, including 93 cases of atypical endometrial hyperplasia (AEH) and 755 cases of endometrial carcinoma. Microsatellite status, MMR protein expression, and gene mutations (MMR, POLE, etc.) were analyzed by histology, IHC, and NGS. Microsatellite status was determined by calculating the MSI-score based on 34 microsatellite loci. An MSI-score<0.3 was defined as microsatellite stable (MSS),≥0.3 as microsatellite instability-high (MSI-H), and 0.3±0.05 as the equivocal range. Simultaneously, a visualization graph was established for minimal microsatellite shift analysis and identification. The 848 lesions included 93 cases of AEH, 442 cases of low-grade endometrioid carcinoma (G1-G2), 143 cases of high-grade endometrioid carcinoma (G3), 20 cases of clear cell carcinoma, 20 cases of carcinosarcoma, 16 cases of mixed adenocarcinoma, 12 cases of dedifferentiated/undifferentiated carcinoma, and 102 cases of other types (including 94 serous carcinomas, 6 mesonephric-like adenocarcinomas, and 2 gastric-type mucinous adenocarcinomas). The results showed that the incidence of dMMR in AEH was 4.3%, and MSI-H was 3.2%, significantly lower than the 24.9% and 23.0% in endometrial cancer, respectively (<0.001). All the 102 cases of other types, including serous carcinoma, were pMMR/MSS. The overall concordance rate between dMMR and MSI-H was 90.6%, but it varied between 75% and 100% across different stages and histological subtypes. In molecular subtyping, the concordance rate was 75% for AEH and carcinosarcoma, 87.5% for dedifferentiated/undifferentiated carcinoma, 91.5% for high-grade endometrioid carcinoma, and 100% for other high-grade carcinomas, while the POLE-mutated subtype had the lowest concordance rate of 66.7%, significantly lower than the 93.1% overall concordance rate for the MSI-H subtype (<0.001). In MSI-H cases, up to 84.5% of endometrial cancer cases exhibited minimal microsatellite shift in at least one locus, with 67.8% showing shifts in≥3 loci. Through analysis of 34 microsatellite loci and visualization, 20 cases (11.5% of 174 MSI-H cases) were identified as borderline (MSI-score=0.3±0.05), considered diagnostically challenging. Among these, MLH1-/PMS2- co-loss accounted for 12/20 cases, with half (6/12) harboring MLH1 mutations; isolated MSH6 loss accounted for 6/20 cases, with 5 of these harboring MSH6 mutations. The 20 minimal shift MSI-H cases shared all pathological features of typical MSI-H endometrial cancer. The incidence and distribution of MSI-H show significant differences across histological subtypes between endometrial precancerous lesions and endometrial carcinomas. The overall concordance between dMMR and MSI-H is good, but varies across different disease stages, histological types, and molecular subtypes. Minimal microsatellite shift is commonly detected in MSI-H cases, and some cases are difficult to interpret due to their classification within the equivocal range. Increasing the number of microsatellite loci, combined with visualization graph comparison and integration of mismatch repair protein immunophenotype and histological features, can effectively improve the accuracy of MSI-H interpretation. - Source: PubMed
Chen T TLiu T QTao XSun Y HZhou X R