-
Je něco špatně v tomto záznamu ?
Microsatellite instability in non-endometrioid ovarian epithelial tumors: a study of 400 cases comparing immunohistochemistry, PCR, and NGS based testing with mutation status of MMR genes
N. Hájková, MK. Bártů, D. Cibula, J. Drozenová, P. Fabian, O. Fadare, F. Frühauf, J. Hausnerová, J. Hojný, E. Krkavcová, J. Laco, SF. Lax, R. Matěj, G. Méhes, R. Michálková, K. Němejcová, N. Singh, S. Stolnicu, M. Švajdler, T. Zima, WG....
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem
- MeSH
- dědičné nepolypózní kolorektální nádory * genetika patologie MeSH
- imunohistochemie MeSH
- lidé MeSH
- mikrosatelitní nestabilita MeSH
- mutace MeSH
- nádory glandulární a epitelové * MeSH
- oprava chybného párování bází DNA genetika MeSH
- polymerázová řetězová reakce MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Testing of microsatellite instability is not only used as a triage for possible Lynch syndrome, but also to predict immunotherapy treatment response. The aim of this study was to assess the frequency of mismatch repair deficiency (MMR-D)/microsatellite instability (MSI) in 400 cases of non-endometrioid ovarian tumors (high-grade serous, low-grade serous, mucinous and clear cell), to compare different methodological approaches of testing, and to assess the optimal approach for next generation sequencing (NGS) MSI testing. For all tumors, we evaluated immunohistochemical (IHC) expression of MMR proteins and assessed microsatellite markers by PCR-based method. Except for high-grade serous carcinoma, we correlated the findings of IHC and PCR with NGS-based MSI testing. We compared the results with somatic and germline mutation in MMR genes. Among the whole cohort, seven MMR-D cases, all clear cell carcinomas (CCC), were found. On PCR analysis, 6 cases were MSI-high and one was MSS. In all cases, mutation of an MMR gene was found; in 2 cases, the mutation was germline (Lynch syndrome). An additional 5 cases with a mutation in MMR gene(s) with MSS status and without MMR-D were identified. We further utilized sequence capture NGS for MSI testing. Employing 53 microsatellite loci provided high sensitivity and specificity. Our study shows that MSI occurs in 7% of CCC while it is rare or absent in other nonendometrioid ovarian neoplasms. Lynch syndrome was present in 2% of patients with CCC. However, some cases with MSH6 mutation can evade all testing methods, including IHC, PCR, and NGS-MSI.
Department of Oncological Pathology Masaryk Memorial Cancer Institute Brno Czech Republic
Department of Pathology Belfast Health and Social Care Trust Belfast United Kingdom
Department of Pathology Faculty of Medicine University of Debrecen Debrecen Hungary
Department of Pathology General Hospital Graz 2 Graz Austria
Department of Pathology University of California San Diego San Diego California
Citace poskytuje Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc23016162
- 003
- CZ-PrNML
- 005
- 20231026110310.0
- 007
- ta
- 008
- 231013s2023 xxu f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1016/j.trsl.2023.05.004 $2 doi
- 035 __
- $a (PubMed)37244485
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xxu
- 100 1_
- $a Hájková, Nikola $u Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
- 245 10
- $a Microsatellite instability in non-endometrioid ovarian epithelial tumors: a study of 400 cases comparing immunohistochemistry, PCR, and NGS based testing with mutation status of MMR genes / $c N. Hájková, MK. Bártů, D. Cibula, J. Drozenová, P. Fabian, O. Fadare, F. Frühauf, J. Hausnerová, J. Hojný, E. Krkavcová, J. Laco, SF. Lax, R. Matěj, G. Méhes, R. Michálková, K. Němejcová, N. Singh, S. Stolnicu, M. Švajdler, T. Zima, WG. McCluggage, I. Stružinská, P. Dundr
- 520 9_
- $a Testing of microsatellite instability is not only used as a triage for possible Lynch syndrome, but also to predict immunotherapy treatment response. The aim of this study was to assess the frequency of mismatch repair deficiency (MMR-D)/microsatellite instability (MSI) in 400 cases of non-endometrioid ovarian tumors (high-grade serous, low-grade serous, mucinous and clear cell), to compare different methodological approaches of testing, and to assess the optimal approach for next generation sequencing (NGS) MSI testing. For all tumors, we evaluated immunohistochemical (IHC) expression of MMR proteins and assessed microsatellite markers by PCR-based method. Except for high-grade serous carcinoma, we correlated the findings of IHC and PCR with NGS-based MSI testing. We compared the results with somatic and germline mutation in MMR genes. Among the whole cohort, seven MMR-D cases, all clear cell carcinomas (CCC), were found. On PCR analysis, 6 cases were MSI-high and one was MSS. In all cases, mutation of an MMR gene was found; in 2 cases, the mutation was germline (Lynch syndrome). An additional 5 cases with a mutation in MMR gene(s) with MSS status and without MMR-D were identified. We further utilized sequence capture NGS for MSI testing. Employing 53 microsatellite loci provided high sensitivity and specificity. Our study shows that MSI occurs in 7% of CCC while it is rare or absent in other nonendometrioid ovarian neoplasms. Lynch syndrome was present in 2% of patients with CCC. However, some cases with MSH6 mutation can evade all testing methods, including IHC, PCR, and NGS-MSI.
- 650 _2
- $a ženské pohlaví $7 D005260
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a mikrosatelitní nestabilita $7 D053842
- 650 _2
- $a imunohistochemie $7 D007150
- 650 12
- $a dědičné nepolypózní kolorektální nádory $x genetika $x patologie $7 D003123
- 650 _2
- $a oprava chybného párování bází DNA $x genetika $7 D053843
- 650 _2
- $a mutace $7 D009154
- 650 _2
- $a polymerázová řetězová reakce $7 D016133
- 650 _2
- $a vysoce účinné nukleotidové sekvenování $7 D059014
- 650 12
- $a nádory glandulární a epitelové $7 D009375
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Bártů, Michaela Kendall $u Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
- 700 1_
- $a Cibula, David $u Department of Obstetrics and Gynecology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
- 700 1_
- $a Drozenová, Jana $u Department of Pathology, Charles University, 3rd Faculty of Medicine, University Hospital Kralovske Vinohrady, Prague, Czech Republic
- 700 1_
- $a Fabian, Pavel $u Department of Oncological Pathology, Masaryk Memorial Cancer Institute, Brno, Czech Republic
- 700 1_
- $a Fadare, Oluwole $u Department of Pathology, University of California San Diego, San Diego, California
- 700 1_
- $a Frühauf, Filip $u Department of Obstetrics and Gynecology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
- 700 1_
- $a Hausnerová, Jitka $u Department of Pathology, University Hospital Brno and Medical Faculty, Masaryk University, Brno, Czech Republic
- 700 1_
- $a Hojný, Jan $u Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
- 700 1_
- $a Krkavcová, Eva $u Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
- 700 1_
- $a Laco, Jan $u The Fingerland Department of Pathology, Charles University, Faculty of Medicine in Hradec Králové and University Hospital Hradec Králové, Czech Republic
- 700 1_
- $a Lax, Sigurd F $u Department of Pathology, General Hospital Graz II, Graz, Austria; Johannes Kepler University Linz, Austria
- 700 1_
- $a Matěj, Radoslav $u Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic; Department of Pathology, Charles University, 3rd Faculty of Medicine, University Hospital Kralovske Vinohrady, Prague, Czech Republic; Department of Pathology and Molecular Medicine, Third Faculty of Medicine, Charles University, Thomayer University Hospital, Prague, Czech Republic
- 700 1_
- $a Méhes, Gábor $u Department of Pathology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
- 700 1_
- $a Michálková, Romana $u Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
- 700 1_
- $a Němejcová, Kristýna $u Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
- 700 1_
- $a Singh, Naveena $u Department of Cellular Pathology, Barts Health NHS Trust, and Blizard Institute of Core Pathology, Queen Mary University of London, London, United Kingdom
- 700 1_
- $a Stolnicu, Simona $u Department of Pathology, George E. Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, Romania
- 700 1_
- $a Švajdler, Marián $u Šikl's Department of Pathology, The Faculty of Medicine and Faculty Hospital in Pilsen, Charles University, Pilsen, Czech Republic
- 700 1_
- $a Zima, Tomáš $u Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
- 700 1_
- $a McCluggage, Wilson Glenn $u Department of Pathology, Belfast Health and Social Care Trust, Belfast, United Kingdom
- 700 1_
- $a Stružinská, Ivana $u Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
- 700 1_
- $a Dundr, Pavel $u Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic. Electronic address: pavel.dundr@vfn.cz
- 773 0_
- $w MED00152122 $t Translational research $x 1878-1810 $g Roč. 260, č. - (2023), s. 61-68
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/37244485 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y - $z 0
- 990 __
- $a 20231013 $b ABA008
- 991 __
- $a 20231026110304 $b ABA008
- 999 __
- $a ok $b bmc $g 1999970 $s 1202524
- BAS __
- $a 3
- BAS __
- $a PreBMC-MEDLINE
- BMC __
- $a 2023 $b 260 $c - $d 61-68 $e 20230525 $i 1878-1810 $m Translational research $n Transl Res $x MED00152122
- LZP __
- $a Pubmed-20231013
