Correlation of immunohistochemical mismatch repair protein status between colorectal carcinoma endoscopic biopsy and resection specimens

2018 ◽  
Vol 71 (7) ◽  
pp. 631-636 ◽  
Author(s):  
Odharnaith O’Brien ◽  
Éanna Ryan ◽  
Ben Creavin ◽  
Michael E Kelly ◽  
Helen M Mohan ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
Endoscopic Biopsy ◽  
Complete Agreement ◽  
Repair System ◽  
Protein Status ◽  
Endoscopic Biopsies ◽  
Repair Protein ◽  
Mismatch Repair System ◽  
Tumour Biopsy ◽  
Deficient Mismatch Repair

BackgroundMicrosatellite instability is reflective of a deficient mismatch repair system (dMMR), which may be due to either sporadic or germline mutations in the relevant mismatch repair (MMR) gene. MMR status is frequently determined by immunohistochemistry (IHC) for mismatch repair proteins (MMRPs) on colorectal cancer (CRC) resection specimens. However, IHC testing performed on endoscopic biopsy may be as reliable as that performed on surgical resections.AimWe aimed to evaluate the reliability of MMR IHC staining on preoperative CRC endoscopic biopsies compared with matched-surgical resection specimens.MethodsA retrospective search of our institution’s histopathology electronic database was performed. Patients with CRC who had MMR IHC performed on both their preoperative endoscopic biopsy and subsequent resection from January 2010 to January 2016 were included. Concordance of MMR staining between biopsy and resection specimens was assessed.ResultsFrom 2000 to 2016, 53 patients had MMR IHC performed on both their preoperative colorectal endoscopic biopsy and resection specimens; 10 patients (18.87%) demonstrated loss of ≥1 MMRP on their initial endoscopic tumour biopsy. The remainder (81.13%) showed preservation of staining for all MMRPs. There was complete agreement in MMR IHC status between the preoperative endoscopic biopsies and corresponding resection specimens in all cases (κ=1.000, P<0.000) with a sensitivity of 100% (95% CI 69.15 to 100) and specificity of 100% (95% CI 91.78 to 100) for detection of dMMR.ConclusionEndoscopic biopsies are a suitable source of tissue for MMR IHC analysis. This may provide a number of advantages to both patients and clinicians in the management of CRC.

scholarly journals Antagonism of Ultraviolet-Light Mutagenesis by the Methyl-Directed Mismatch-Repair System of Escherichia coli

Genetics ◽  
2000 ◽  
Vol 154 (2) ◽  
pp. 503-512 ◽  
Author(s):  
Hongbo Liu ◽  
Stephen R Hewitt ◽  
John B Hays
Keyword(s):  
Escherichia Coli ◽  
Mismatch Repair ◽  
Excision Repair ◽  
Spontaneous Mutation ◽  
Repair System ◽  
Uv Mutagenesis ◽  
Repair Protein ◽  
Mismatch Repair System

Abstract Previous studies have demonstrated that the Escherichia coli MutHLS mismatch-repair system can process UV-irradiated DNA in vivo and that the human MSH2·MSH6 mismatch-repair protein binds more strongly in vitro to photoproduct/base mismatches than to “matched” photoproducts in DNA. We tested the hypothesis that mismatch repair directed against incorrect bases opposite photoproducts might reduce UV mutagenesis, using two alleles at E. coli lacZ codon 461, which revert, respectively, via CCC → CTC and CTT → CTC transitions. F′ lacZ targets were mated from mut+ donors into mutH, mutL, or mutS recipients, once cells were at substantial densities, to minimize spontaneous mutation prior to irradiation. In umu+ mut+ recipients, a range of UV fluences induced lac+ revertant frequencies of 4–25 × 10−8; these frequencies were consistently 2-fold higher in mutH, mutL, or mutS recipients. Since this effect on mutation frequency was unaltered by an Mfd− defect, it appears not to involve transcription-coupled excision repair. In mut+ umuC122::Tn5 bacteria, UV mutagenesis (at 60 J/m2) was very low, but mutH or mutL or mutS mutations increased reversion of both lacZ alleles roughly 25-fold, to 5–10 × 10−8. Thus, at UV doses too low to induce SOS functions, such as Umu2′D, most incorrect bases opposite occasional photoproducts may be removed by mismatch repair, whereas in heavily irradiated (SOS-induced) cells, mismatch repair may only correct some photoproduct/base mismatches, so UV mutagenesis remains substantial.

Association between deficient mismatch repair system and efficacy to irinotecan-containing chemotherapy in metastatic colon cancer

2011 ◽  
Vol 102 (9) ◽  
pp. 1706-1711 ◽  
Author(s):  
Jeong Eun Kim ◽  
Yong Sang Hong ◽  
Min-Hee Ryu ◽  
Jae-Lyun Lee ◽  
Heung Moon Chang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Mismatch Repair ◽  
Repair System ◽  
Metastatic Colon Cancer ◽  
Mismatch Repair System ◽  
Deficient Mismatch Repair

scholarly journals Deficient mismatch repair system in patients with sporadic advanced colorectal cancer

2009 ◽  
Vol 100 (2) ◽  
pp. 266-273 ◽  
Author(s):  
M Koopman ◽  
G A M Kortman ◽  
L Mekenkamp ◽  
M J L Ligtenberg ◽  
N Hoogerbrugge ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mismatch Repair ◽  
Advanced Colorectal Cancer ◽  
Repair System ◽  
Mismatch Repair System ◽  
Deficient Mismatch Repair

The Genetics of Hereditary Non-Polyposis Colorectal Cancer

2003 ◽  
Vol 1 (1) ◽  
pp. 137-144 ◽  
Author(s):  
Stephen B. Gruber ◽  
Wendy Kohlmann
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Molecular Diagnostic ◽  
Repair System ◽  
Molecular Fingerprint ◽  
Dna Mismatch ◽  
Repair Protein ◽  
Mismatch Repair System ◽  
Defective Mismatch Repair

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant condition accounting for 3% to 5% of all colorectal cancer. HNPCC is caused by germline mutations in the mismatch repair system and is recognized by a characteristic clinical phenotype as well as a hallmark of the tumors termed “microsatellite instability.” Microsatellite instability serves as a molecular fingerprint for defective mismatch repair and has proven to be useful in the molecular diagnostic workup for HNPCC. The crystal structure of the DNA mismatch repair protein MutS has been solved, providing insight into the molecular basis of defective mismatch repair. Genetic testing has become a key component of the treatment of patients and families with HNPCC, and enhanced surveillance for HNPCC has been shown to reduce the rate of colorectal cancer by more than half and improve 10-year survival from 68% to 93%.

Functional Specifics of the MutL Protein of the DNA Mismatch Repair System in Different Organisms

2020 ◽  
Vol 46 (6) ◽  
pp. 875-890
Author(s):  
M. V. Monakhova ◽  
M. A. Milakina ◽  
R. M. Trikin ◽  
T. S. Oretskaya ◽  
E. A. Kubareva
Keyword(s):  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Repair System ◽  
Dna Mismatch ◽  
Dna Mismatch Repair System ◽  
Mismatch Repair System

scholarly journals Poorly Repaired Mismatches in Heteroduplex DNA are Hyper-Recombinagenic in Saccharomyces cerevisiae

Genetics ◽  
1996 ◽  
Vol 142 (2) ◽  
pp. 407-416 ◽  
Author(s):  
P Manivasakam ◽  
Susan M Rosenberg ◽  
P J Hastings
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Mismatch Repair ◽  
Genetic Markers ◽  
Meiotic Recombination ◽  
Repair System ◽  
Normal Allele ◽  
Heteroduplex Dna ◽  
Mismatch Repair System ◽  
Postmeiotic Segregation ◽  
System Operating

Abstract In yeast meiotic recombination, alleles used as genetic markers fall into two classes as regards their fate when incorporated into heteroduplex DNA. Normal alleles are those that form heteroduplexes that are nearly always recognized and corrected by the mismatch repair system operating in meiosis. High PMS (postmeiotic segregation) alleles form heteroduplexes that are inefficiently mismatch repaired. We report that placing any of several high PMS alleles very close to normal alleles causes hyperrecombination between these markers. We propose that this hyperrecombination is caused by the high PMS allele blocking a mismatch repair tract initiated from the normal allele, thus preventing corepair of the two alleles, which would prevent formation of recombinants. The results of three point crosses involving two PMS alleles and a normal allele suggest that high PMS alleles placed between two alleles that are normally corepaired block that corepair.

scholarly journals Saturation of DNA Mismatch Repair and Error Catastrophe by a Base Analogue in Escherichia coli

Genetics ◽  
2002 ◽  
Vol 161 (4) ◽  
pp. 1363-1371
Author(s):  
Kazuo Negishi ◽  
David Loakes ◽  
Roel M Schaaper
Keyword(s):  
Escherichia Coli ◽  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Repair System ◽  
Mutagenic Action ◽  
Wild Type ◽  
Dna Mismatch ◽  
Cell Counts ◽  
Error Catastrophe ◽  
Mismatch Repair System

Abstract Deoxyribosyl-dihydropyrimido[4,5-c][1,2]oxazin-7-one (dP) is a potent mutagenic deoxycytidine-derived base analogue capable of pairing with both A and G, thereby causing G · C → A · T and A · T → G · C transition mutations. We have found that the Escherichia coli DNA mismatch-repair system can protect cells against this mutagenic action. At a low dose, dP is much more mutagenic in mismatch-repair-defective mutH, mutL, and mutS strains than in a wild-type strain. At higher doses, the difference between the wild-type and the mutator strains becomes small, indicative of saturation of mismatch repair. Introduction of a plasmid containing the E. coli mutL+ gene significantly reduces dP-induced mutagenesis. Together, the results indicate that the mismatch-repair system can remove dP-induced replication errors, but that its capacity to remove dP-containing mismatches can readily be saturated. When cells are cultured at high dP concentration, mutant frequencies reach exceptionally high levels and viable cell counts are reduced. The observations are consistent with a hypothesis in which dP-induced cell killing and growth impairment result from excess mutations (error catastrophe), as previously observed spontaneously in proofreading-deficient mutD (dnaQ) strains.

scholarly journals Steady-state regulation of the human DNA mismatch repair system.

2000 ◽  
Vol 275 (37) ◽  
pp. 29178
Author(s):  
Dong Kyung Chang ◽  
Luigi Ricciardiello ◽  
Ajay Goel ◽  
Christina L. Chang ◽  
C. Richard Boland
Keyword(s):  
Steady State ◽  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
State Regulation ◽  
Repair System ◽  
Dna Mismatch ◽  
Human Dna ◽  
Dna Mismatch Repair System ◽  
Mismatch Repair System
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