What is hiding behind S100 protein and SOX10 positive oncocytomas? Oncocytic pleomorphic adenoma and myoepithelioma with novel gene fusions in a subset of cases
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11140%2F20%3A10413152" target="_blank" >RIV/00216208:11140/20:10413152 - isvavai.cz</a>
Výsledek na webu
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=oqvmqvxU4k" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=oqvmqvxU4k</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.humpath.2020.07.009" target="_blank" >10.1016/j.humpath.2020.07.009</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
What is hiding behind S100 protein and SOX10 positive oncocytomas? Oncocytic pleomorphic adenoma and myoepithelioma with novel gene fusions in a subset of cases
Popis výsledku v původním jazyce
Oncocytomas (OC) in salivary glands are rare benign tumors composed of mitochondria-rich epithelial cells (oncocytes), mostly localized in the parotid gland. The treatment of choice is simple excision. Extensive oncocytic metaplasia of pleomorphic adenoma (PA) and myoepithelioma (ME) can be diagnostically challenging and may camouflage the correct diagnosis. These tumors should be treated more carefully compared to OC, given the risk of frequent recurrences and the possibility of malignant transformation. We have investigated 89 oncocytic lesions from our files, including OC (n=74) and metaplastic oncocytic variant of PA/ME (n=15). All OCs were stained for S100 protein and SOX10. The tumors with immunohistochemical expression of one or both markers were tested by next-generation sequencing (NGS). NGS results were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and/or fluorescence in situ hybridization (FISH). Ten cases originally diagnosed as OC and one low-grade uncertain oncocytic tumor (11/74) revealed nuclear-cytoplasmic and/or nuclear positivity for S100 protein and/or SOX10, respectively. Fusion transcripts CHCHD7-PLAG1 and GEM-PLAG1 were found in two cases (one fusion in each), and these were confirmed by RT-PCR and PLAG1 break-apart FISH probe, respectively. Another five cases were positive for PLAG1 rearrangement by FISH. In the control group of 15 oncocytic PA/ME, 4/15 tested tumors harbored gene fusions including NFT3-PLAG1, CHCHD7-PLAG1, FBXO32-PLAG1, and C1orf116-PLAG1 (one fusion in each case) as detected by NGS. Two fusions were confirmed by RT-PCR, one case by FISH and one case was not analyzable by FISH. We additionally tested 24 OCs negative for S100 protein and SOX10 by IHC and by FISH for rearrangement of PLAG1 gene, but none of them were positive. SOX10 and/or S100 protein immunopositivity in conjunction with rearrangement of the PLAG1 gene assisted in reclassification of a subset of oncocytomas as oncocytic variants of PA and ME. Therefore, we recommend to include S100 protein and SOX10 IHC when diagnosing tumors with predominantly oncocytoma-like differentiation. In addition, by NGS three new gene fusions were detected in oncocytic ME including NTF3-PLAG1, FBXO32-PLAG1, and GEM-PLAG1, and a new fusion C1orf116-PLAG1 was detected in oncocytic PA.
Název v anglickém jazyce
What is hiding behind S100 protein and SOX10 positive oncocytomas? Oncocytic pleomorphic adenoma and myoepithelioma with novel gene fusions in a subset of cases
Popis výsledku anglicky
Oncocytomas (OC) in salivary glands are rare benign tumors composed of mitochondria-rich epithelial cells (oncocytes), mostly localized in the parotid gland. The treatment of choice is simple excision. Extensive oncocytic metaplasia of pleomorphic adenoma (PA) and myoepithelioma (ME) can be diagnostically challenging and may camouflage the correct diagnosis. These tumors should be treated more carefully compared to OC, given the risk of frequent recurrences and the possibility of malignant transformation. We have investigated 89 oncocytic lesions from our files, including OC (n=74) and metaplastic oncocytic variant of PA/ME (n=15). All OCs were stained for S100 protein and SOX10. The tumors with immunohistochemical expression of one or both markers were tested by next-generation sequencing (NGS). NGS results were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and/or fluorescence in situ hybridization (FISH). Ten cases originally diagnosed as OC and one low-grade uncertain oncocytic tumor (11/74) revealed nuclear-cytoplasmic and/or nuclear positivity for S100 protein and/or SOX10, respectively. Fusion transcripts CHCHD7-PLAG1 and GEM-PLAG1 were found in two cases (one fusion in each), and these were confirmed by RT-PCR and PLAG1 break-apart FISH probe, respectively. Another five cases were positive for PLAG1 rearrangement by FISH. In the control group of 15 oncocytic PA/ME, 4/15 tested tumors harbored gene fusions including NFT3-PLAG1, CHCHD7-PLAG1, FBXO32-PLAG1, and C1orf116-PLAG1 (one fusion in each case) as detected by NGS. Two fusions were confirmed by RT-PCR, one case by FISH and one case was not analyzable by FISH. We additionally tested 24 OCs negative for S100 protein and SOX10 by IHC and by FISH for rearrangement of PLAG1 gene, but none of them were positive. SOX10 and/or S100 protein immunopositivity in conjunction with rearrangement of the PLAG1 gene assisted in reclassification of a subset of oncocytomas as oncocytic variants of PA and ME. Therefore, we recommend to include S100 protein and SOX10 IHC when diagnosing tumors with predominantly oncocytoma-like differentiation. In addition, by NGS three new gene fusions were detected in oncocytic ME including NTF3-PLAG1, FBXO32-PLAG1, and GEM-PLAG1, and a new fusion C1orf116-PLAG1 was detected in oncocytic PA.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
30109 - Pathology
Návaznosti výsledku
Projekt
—
Návaznosti
S - Specificky vyzkum na vysokych skolach
Ostatní
Rok uplatnění
2020
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Human Pathology
ISSN
0046-8177
e-ISSN
—
Svazek periodika
103
Číslo periodika v rámci svazku
July
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
11
Strana od-do
52-62
Kód UT WoS článku
000575855100006
EID výsledku v databázi Scopus
2-s2.0-85089530613