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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00669806%3A_____%2F23%3A10464753" target="_blank" >RIV/00669806:_____/23:10464753 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14110/23:00131347 RIV/00209805:_____/23:00079315 RIV/00216208:11110/23:10464753 RIV/00216208:11120/23:43925630 a 7 dalších

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=0nb4JFAkTy" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=0nb4JFAkTy</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.trsl.2023.05.004" target="_blank" >10.1016/j.trsl.2023.05.004</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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, six cases were MSI-high and one was MSS. In all cases, mutation of an MMR gene was found; in two cases, the mutation was germline (Lynch syndrome). An additional five 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 non-endometrioid 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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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, six cases were MSI-high and one was MSS. In all cases, mutation of an MMR gene was found; in two cases, the mutation was germline (Lynch syndrome). An additional five 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 non-endometrioid 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Translational Research

ISSN

1931-5244

e-ISSN

1878-1810

Svazek periodika

260

Číslo periodika v rámci svazku

October

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

8

Strana od-do

61-68

Kód UT WoS článku

001067763800001

EID výsledku v databázi Scopus

2-s2.0-85163358484