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

J 2023

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

HÁJKOVÁ, Nikola, Michaela BÁRTŮ KENDALL, David CIBULA, Jana DROZENOVÁ, Pavel FABIAN et. al.

Basic information

Original name

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

Authors

HÁJKOVÁ, Nikola (203 Czech Republic), Michaela BÁRTŮ KENDALL (203 Czech Republic), David CIBULA (203 Czech Republic), Jana DROZENOVÁ (203 Czech Republic), Pavel FABIAN (203 Czech Republic), Oluwole FADARE, Filip FRÜHAUF (203 Czech Republic), Jitka HAUSNEROVÁ (203 Czech Republic, belonging to the institution), Jan HOJNÝ (203 Czech Republic), Eva KRKAVCOVÁ (203 Czech Republic), Jan LACO (203 Czech Republic), Sigurd F LAX, Radoslav MATĚJ (203 Czech Republic), Gábor MÉHES, Romana MICHÁLKOVÁ (203 Czech Republic), Kristýna NĚMEJCOVÁ (203 Czech Republic), Naveena SINGH, Simona STOLNICU (203 Czech Republic), Marián ŠVAJDLER (203 Czech Republic), Tomáš ZIMA (203 Czech Republic), Wilson Glenn MCCLUGGAGE, Ivana STRUŽINSKÁ (203 Czech Republic) and Pavel DUNDR (203 Czech Republic)

Edition

Translational research, NEW YORK, ELSEVIER SCIENCE INC, 2023, 1931-5244

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30109 Pathology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 7.800 in 2022

RIV identification code

RIV/00216224:14110/23:00131347

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/j.trsl.2023.05.004

UT WoS

001067763800001

Keywords in English

non-endometrioid ovarian epithelial tumors; microsatellite instability

Abstract

V originále

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.

Links

90233, large research infrastructures

Name: BBMRI.cz IV

Citovat

HÁJKOVÁ, Nikola, Michaela BÁRTŮ KENDALL, David CIBULA, Jana DROZENOVÁ, Pavel FABIAN, Oluwole FADARE, Filip FRÜHAUF, Jitka HAUSNEROVÁ, Jan HOJNÝ, Eva KRKAVCOVÁ, Jan LACO, Sigurd F LAX, Radoslav MATĚJ, Gábor MÉHES, Romana MICHÁLKOVÁ, Kristýna NĚMEJCOVÁ, Naveena SINGH, Simona STOLNICU, Marián ŠVAJDLER, Tomáš ZIMA, Wilson Glenn MCCLUGGAGE, Ivana STRUŽINSKÁ and Pavel DUNDR. 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. Translational research. NEW YORK: ELSEVIER SCIENCE INC, 2023, vol. 260, Ocotber 2023, p. 61-68. ISSN 1931-5244. Available from: https://dx.doi.org/10.1016/j.trsl.2023.05.004.

@article{2300438,
   author = {Hájková, Nikola and Bártů Kendall, Michaela and Cibula, David and Drozenová, Jana and Fabian, Pavel and Fadare, Oluwole and Frühauf, Filip and Hausnerová, Jitka and Hojný, Jan and Krkavcová, Eva and Laco, Jan and Lax, Sigurd F and Matěj, Radoslav and Méhes, Gábor and Michálková, Romana and Němejcová, Kristýna and Singh, Naveena and Stolnicu, Simona and Švajdler, Marián and Zima, Tomáš and McCluggage, Wilson Glenn and Stružinská, Ivana and Dundr, Pavel},
   article_location = {NEW YORK},
   article_number = {Ocotber 2023},
   doi = {http://dx.doi.org/10.1016/j.trsl.2023.05.004},
   keywords = {non-endometrioid ovarian epithelial tumors; microsatellite instability},
   language = {eng},
   issn = {1931-5244},
   journal = {Translational research},
   title = {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},
   url = {https://www.sciencedirect.com/science/article/pii/S1931524423000890?via%3Dihub},
   volume = {260},
   year = {2023}
}

TY  - JOUR
ID  - 2300438
AU  - Hájková, Nikola - Bártů Kendall, Michaela - Cibula, David - Drozenová, Jana - Fabian, Pavel - Fadare, Oluwole - Frühauf, Filip - Hausnerová, Jitka - Hojný, Jan - Krkavcová, Eva - Laco, Jan - Lax, Sigurd F - Matěj, Radoslav - Méhes, Gábor - Michálková, Romana - Němejcová, Kristýna - Singh, Naveena - Stolnicu, Simona - Švajdler, Marián - Zima, Tomáš - McCluggage, Wilson Glenn - Stružinská, Ivana - Dundr, Pavel
PY  - 2023
TI  - 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
JF  - Translational research
VL  - 260
IS  - Ocotber 2023
SP  - 61-68
EP  - 61-68
PB  - ELSEVIER SCIENCE INC
SN  - 19315244
KW  - non-endometrioid ovarian epithelial tumors
KW  - microsatellite instability
UR  - https://www.sciencedirect.com/science/article/pii/S1931524423000890?via%3Dihub
N2  - 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.
ER  -

HÁJKOVÁ, Nikola, Michaela BÁRTŮ KENDALL, David CIBULA, Jana DROZENOVÁ, Pavel FABIAN, Oluwole FADARE, Filip FRÜHAUF, Jitka HAUSNEROVÁ, Jan HOJNÝ, Eva KRKAVCOVÁ, Jan LACO, Sigurd F LAX, Radoslav MATĚJ, Gábor MÉHES, Romana MICHÁLKOVÁ, Kristýna NĚMEJCOVÁ, Naveena SINGH, Simona STOLNICU, Marián ŠVAJDLER, Tomáš ZIMA, Wilson Glenn MCCLUGGAGE, Ivana STRUŽINSKÁ and Pavel DUNDR. 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. \textit{Translational research}. NEW YORK: ELSEVIER SCIENCE INC, 2023, vol.~260, Ocotber 2023, p.~61-68. ISSN~1931-5244. Available from: https://dx.doi.org/10.1016/j.trsl.2023.05.004.

Detailed Information on Publication Record