Refer to the appropriate VENTANA detection kit method sheet for detailed descriptions of: Principle of the Procedure, Material and Methods, Specimen Collection and Preparation for Analysis, Quality Control Procedures, Troubleshooting, Interpretation of Results, and Limitations.",
"Language": "en",
"Country": "XG",
"Code": "Content"
},
{
"Name": "Background Information",
"Value": "VENTANA anti-MSH6 (SP93) antibody is a rabbit monoclonal antibody produced against a synthetic peptide corresponding to an internal region of human MSH6 protein. Colorectal cancer is the third most common cancer and the fourth most prevalent cause of cancer death in the world.1 The majority of CRCs show chromosomal instability, however approximately 15% of cancers develop through an alternative pathway characterized by defective function of the DNA mismatch repair (MMR) system. As a consequence of the MMR deficiency, tumors exhibit microsatellite instability (MSI) resulting from the inability of MMR proteins to repair DNA replication errors. CRCs with MMR defects are denoted as deficient MMR (dMMR) tumors. In contrast, CRCs with no MMR defects are denoted as proficient MMR (pMMR) tumors. The dMMR colorectal cancers are often poorly differentiated and frequently show proximal colon predominance, mucinous, medullary, or signet ring histologic features and increased numbers of tumor-infiltrating lymphocytes.2,3 In general, MMR deficiency may be caused either by germline mutations in one of the MMR genes with subsequent loss of the corresponding normal allele through genetic or epigenetic mechanisms, somatic mutations in the alleles, or by epigenetic inactivation of the MLH1 gene through methylation.4 The four most commonly mutated MMR genes are MLH1, PMS2, MSH2, and MSH6. In normal cells, the MLH1 protein forms a complex (heterodimer) with the PMS2 protein, while the MSH2 protein forms a complex with the MSH6 protein.5,6 When DNA mismatches occur, the MSH2/MSH6 heterodimer binds to the mismatched DNA, inducing a conformational change. The MLH1/PMS2 heterodimer binds the DNA-bound MSH2/MSH6 complex resulting in excision repair of the affected DNA. The MLH1, PMS2, MSH2, and MSH6 proteins are clinically important MMR proteins encoded by genes that may be mutated in families with Lynch syndrome.7,8 Carriers of these mutations have a high lifetime risk of developing colorectal and other cancers due to accumulation of DNA replication errors in proliferating cells. Lynch syndrome represents 1- 6% of all CRCs. These tumors result from the inheritance of a germline autosomal dominant mutation in one of the four MMR genes, with MLH1 loss occurring in the majority of these Lynch syndrome associated CRCs.5,9,10 More than 300 different mutations in the MMR family of proteins have been identified in patients with Lynch syndrome. The Lynch syndrome-associated tumor phenotype is generally characterized by immunohistochemical loss of expression in MMR proteins, particularly MLH1, PMS2, MSH2, and MSH6.10-13 MMR IHC testing has been shown to be useful in the identification of the specific MMR gene in which either a germline or a somatic alteration is most likely to be found.14 As part of the VENTANA MMR IHC Panel, VENTANA anti-BRAF V600E (VE1) Mouse Monoclonal Primary Antibody (VENTANA anti-BRAF V600E (VE1) antibody) aids to differentiate sporadic and probable Lynch syndrome CRC in the absence of MLH1 protein expression.15,16 In CRC, loss of MLH1 protein is frequently the result of hypermethylation of the MLH1 promoter and indicates a sporadic occurrence.17 The presence of the BRAF V600E protein is tightly linked with hypermethylation of the MLH1 promoter. As a result, a positive staining result with VENTANA anti-BRAF V600E (VE1) antibody indicates sporadic CRC.
1. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray, F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. 2. Geiersbach KB, Samowitz WS. Microsatellite instability and colorectal cancer. Arch Pathol Lab Med. 2011;135(10):1269-1277. 3. Wright CL, Stewart ID. Histopathology and mismatch repair status of 458 consecutive colorectal carcinomas. Am J Surg Pathol. 2003;27(11):1393-1406. 4. Tiwari AK, Roy HK, Lynch HT. Lynch syndrome in the 21st century: clinical perspectives. QJM. 2016;109(3):151-158. 5. Buza N, Ziai J, Hui P. Mismatch repair deficiency testing in clinical practice. Expert Rev Mol Diagn. 2016;16(5):591-604. 6. Silva FCC, Torrezan GT, Ferreira JRO, Oliveira LP, Begnami M, et al. Germline Mutations in MLH1 Leading to Isolated Loss of PMS2 Expression in Lynch Syndrome: Implications for Diagnostics in the Clinic. Am J Surg Pathol. 2017;41(6):861-864. 7. Boyer JC, Umar A, Risinger JI, Lipford JR, Kane M, et al. Microsatellite instability, mismatch repair deficiency, and genetic defects in human cancer cell lines. Cancer Res. 1995;55(24):6063-6070. 8. Lawes DA, Pearson T, Sengupta S, Boulos PB. The role of MLH1, MSH2 and MSH6 in the development of multiple colorectal cancers. Br J Cancer. 2005;93(4):472-477. 9. Lynch HT, de la Chapelle A. Hereditary colorectal cancer. N Engl J Med. 2003;348(10):919-932. 10. Peltomaki P. Role of DNA mismatch repair defects in the pathogenesis of human cancer. J Clin Oncol. 2003;21(6):1174-1179. 11. Lynch HT, Smyrk T. Hereditary nonpolyposis colorectal cancer (Lynch syndrome). An updated review. Cancer. 1996;78(6):1149-1167. 12. Caldes T, Godino J, Sanchez A, Corbacho C, De la Hoya M, et al. Immunohistochemistry and microsatellite instability testing for selecting MLH1, MSH2 and MSH6 mutation carriers in hereditary non-polyposis colorectal cancer. Oncol Rep. 2004;12(3):621-629. 13. Shia J, Klimstra DS, Nafa K, Offit K, Guillem JG, et al. Value of immunohistochemical detection of DNA mismatch repair proteins in predicting germline mutation in hereditary colorectal neoplasms. Am J Surg Pathol. 2005;29(1):96-104. 14. Cunningham JM, Tester DJ, Thibodeau SN. Mutation detection in colorectal cancers : direct sequencing of DNA mismatch repair genes. Methods Mol Med. 2001;50:87- 98. 15. Domingo E, Laiho P, Ollikainen M, Pinto M, Wang L, et al. BRAF screening as a low-cost effective strategy for simplifying HNPCC genetic testing. J Med Genet. 2004;41(9):664-668. 16. Jin M, Hampel H, Zhou X, Schunemann L, Yearsley M, et al. BRAF V600E mutation analysis simplifies the testing algorithm for Lynch syndrome. Am J Clin Pathol. 2013;140(2):177-183. 17. Deng G, Bell I, Crawley S, Gum J, Terdiman JP, et al. BRAF mutation is frequently present in sporadic colorectal cancer with methylated hMLH1, but not in hereditary nonpolyposis colorectal cancer. Clin Cancer Res. 2004;10(1 Pt 1):191-195.",
"Language": "en",
"Country": "XG",
"Code": "Background Information"
},
{
"Name": "Intended Use",
"Value": "Le VENTANA anti-MSH6 (SP93) Rabbit Monoclonal Primary Antibody (anticorps VENTANA anti-MSH6 [SP93]) est destiné à être utilisé pour la détection qualitative de la protéine MSH6 dans des coupes de tissus fixés au formol et inclus en paraffine. L’anticorps VENTANA anti-MSH6 (SP93) est un produit prêt à l’emploi sur les appareils BenchMark ULTRA, XT et GX en association avec l’OptiView DAB IHC Detection Kit et des réactifs auxiliaires.
L’anticorps VENTANA anti-MSH6 (SP93) fait partie du VENTANA MMR IHC Panel, qui comprend le VENTANA anti-MLH1 (M1) Mouse Monoclonal Primary Antibody, le VENTANA anti-PMS2 (A16-4) Mouse Monoclonal Primary Antibody, le VENTANA anti-MSH2 (G219-1129) Mouse Monoclonal Primary Antibody et le VENTANA anti-BRAF V600E (VE1) Mouse Monoclonal Primary Antibody. Le VENTANA MMR IHC Panel est indiqué pour la détection d’une déficience en protéines de réparation des mésappariements en vue d’identifier les individus présentant un risque de syndrome de Lynch parmi les patients atteints de cancer colorectal (CRC) et, en cas de statut BRAF V600E, pour faciliter la distinction entre les CRC sporadiques et les CRC probablement dus au syndrome de Lynch en l’absence d’expression de la protéine MLH1.
Ces produits doivent être interprétés par un anatomopathologiste qualifié, en complément d’examens histologiques, d’informations cliniques pertinentes et de contrôles adaptés.
Cet anticorps est conçu pour une utilisation en diagnostic in vitro (IVD).",
"Language": "fr",
"Country": "XG",
"Code": "Intended Use"
},
{
"Name": "Principle",
"Value": "The VENTANA anti-MSH6 (SP93) antibody is a rabbit monoclonal antibody produced against a synthetic peptide corresponding to an internal region of human MSH6 protein. The VENTANA anti-MSH6 (SP93) antibody binds to MSH6 protein in FFPE tissue sections. The antibody can be localized using a haptenated secondary antibody followed by a multimer anti-hapten-HRP conjugate (OptiView DAB IHC Detection Kit, Cat. No. 760- 700 / 06396500001). The specific antibody-enzyme complex is then visualized with a precipitating enzyme reaction product. Each step is incubated for a precise time and temperature. At the end of each incubation step, the BenchMark ULTRA instrument washes the sections to stop the reaction and to remove unbound material that would hinder the desired reaction in subsequent steps. It also applies ULTRA LCS (Predilute), (Cat. No. 650-210 / 05424534001) or LCS (Predilute) (Cat. No. 650-010 / 05264839001), which minimizes evaporation of the aqueous reagents from the specimen slide. ",
"Language": "en",
"Country": "XG",
"Code": "Principle"
},
{
"Name": "Product Purpose",
"Value": "Le VENTANA anti-MSH6 (SP93) Rabbit Monoclonal Primary Antibody (anticorps VENTANA anti-MSH6 [SP93]) est destiné à être utilisé pour la détection qualitative de la protéine MSH6 dans des coupes de tissus fixés au formol et inclus en paraffine. L’anticorps VENTANA anti-MSH6 (SP93) est un produit prêt à l’emploi sur les appareils BenchMark ULTRA, XT et GX en association avec l’OptiView DAB IHC Detection Kit et des réactifs auxiliaires.
L’anticorps VENTANA anti-MSH6 (SP93) fait partie du VENTANA MMR IHC Panel, qui comprend le VENTANA anti-MLH1 (M1) Mouse Monoclonal Primary Antibody, le VENTANA anti-PMS2 (A16-4) Mouse Monoclonal Primary Antibody, le VENTANA anti-MSH2 (G219-1129) Mouse Monoclonal Primary Antibody et le VENTANA anti-BRAF V600E (VE1) Mouse Monoclonal Primary Antibody. Le VENTANA MMR IHC Panel est indiqué pour la détection d’une déficience en protéines de réparation des mésappariements en vue d’identifier les individus présentant un risque de syndrome de Lynch parmi les patients atteints de cancer colorectal (CRC) et, en cas de statut BRAF V600E, pour faciliter la distinction entre les CRC sporadiques et les CRC probablement dus au syndrome de Lynch en l’absence d’expression de la protéine MLH1.
Ces produits doivent être interprétés par un anatomopathologiste qualifié, en complément d’examens histologiques, d’informations cliniques pertinentes et de contrôles adaptés.
Cet anticorps est conçu pour une utilisation en diagnostic in vitro (IVD).",
"Language": "fr",
"Country": "XG",
"Code": "Product Purpose"
}
]
}
}
]
}
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