Genomic profiling of dedifferentiated endometrial carcinomas arising in the background of high-grade carcinoma : a targeted next-generation sequencing study
© 2023 The Authors. Histopathology published by John Wiley & Sons Ltd..
AIMS: Our understanding of dedifferentiated endometrial carcinoma (DEC), a rare and aggressive malignancy, mainly reflects undifferentiated carcinomas (UC) arising in the setting of low-grade endometrial cancer (DEC-LG). However, cases of UC arising in the setting of high-grade EC (DEC-HG) have been noted in the literature. Our knowledge of the genomics of DEC-HG is limited. To characterise the molecular landscape of DEC-HC, targeted genomic sequencing and immunohistochemical analysis was carried out on seven DEC-HG and four DEC-LG.
METHODS AND RESULTS: DEC-HG and DEC-LG, including undifferentiated and differentiated components, both showed a similar frequency and spectrum of mutations. ARID1A mutations were identified in 6/7 (86%) DEC-HG and 4/4 (100%) DEC-LG, while SMARCA4 mutations were present in 4/7 (57%) DEC-HG and in 1/4 (25%) DEC-LG. Concurrent SMARCA4/BRG1 protein loss by immunohistochemistry was observed in 3/4 and 1/1 SMARCA4 mutated DEC-HG and DEC-LG, respectively. Neither genomic alterations nor protein loss in SMARCB1/INI1 were observed in any of our cases. TP53 mutations were detected in 4/7 (57%) DEC-HG and in 2/4 (50%) DEC-LG, while mutation-pattern p53 immunohistochemistry expression was observed in 2/7 (29%) DEC-HG and none of the DEC-LG. MLH1 mutations were observed in 1/7 (14%) DEC-HG and 1/4 (25%) DEC-LG. MSH2 and MSH6 mutations were each detected in 1/7 (14%) DEC-HG, but neither was associated with corresponding loss of protein expression.
CONCLUSION: The findings support expanding the definition of DEC to include DEC-HG, a previously under-recognised phenomenon with genomic similarities to DEC-LG.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:83 |
|---|---|
| Enthalten in: |
Histopathology - 83(2023), 3 vom: 01. Sept., Seite 366-375 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Olkhov-Mitsel, Ekaterina [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 11.08.2023 Date Revised 11.08.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1111/his.14938 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM357245946 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM357245946 | ||
| 003 | DE-627 | ||
| 005 | 20231226072153.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1111/his.14938 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1190.xml |
| 035 | |a (DE-627)NLM357245946 | ||
| 035 | |a (NLM)37222195 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Olkhov-Mitsel, Ekaterina |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Genomic profiling of dedifferentiated endometrial carcinomas arising in the background of high-grade carcinoma |b a targeted next-generation sequencing study |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 11.08.2023 | ||
| 500 | |a Date Revised 11.08.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 The Authors. Histopathology published by John Wiley & Sons Ltd. | ||
| 520 | |a AIMS: Our understanding of dedifferentiated endometrial carcinoma (DEC), a rare and aggressive malignancy, mainly reflects undifferentiated carcinomas (UC) arising in the setting of low-grade endometrial cancer (DEC-LG). However, cases of UC arising in the setting of high-grade EC (DEC-HG) have been noted in the literature. Our knowledge of the genomics of DEC-HG is limited. To characterise the molecular landscape of DEC-HC, targeted genomic sequencing and immunohistochemical analysis was carried out on seven DEC-HG and four DEC-LG | ||
| 520 | |a METHODS AND RESULTS: DEC-HG and DEC-LG, including undifferentiated and differentiated components, both showed a similar frequency and spectrum of mutations. ARID1A mutations were identified in 6/7 (86%) DEC-HG and 4/4 (100%) DEC-LG, while SMARCA4 mutations were present in 4/7 (57%) DEC-HG and in 1/4 (25%) DEC-LG. Concurrent SMARCA4/BRG1 protein loss by immunohistochemistry was observed in 3/4 and 1/1 SMARCA4 mutated DEC-HG and DEC-LG, respectively. Neither genomic alterations nor protein loss in SMARCB1/INI1 were observed in any of our cases. TP53 mutations were detected in 4/7 (57%) DEC-HG and in 2/4 (50%) DEC-LG, while mutation-pattern p53 immunohistochemistry expression was observed in 2/7 (29%) DEC-HG and none of the DEC-LG. MLH1 mutations were observed in 1/7 (14%) DEC-HG and 1/4 (25%) DEC-LG. MSH2 and MSH6 mutations were each detected in 1/7 (14%) DEC-HG, but neither was associated with corresponding loss of protein expression | ||
| 520 | |a CONCLUSION: The findings support expanding the definition of DEC to include DEC-HG, a previously under-recognised phenomenon with genomic similarities to DEC-LG | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Dedifferentiated endometrial cancer | |
| 650 | 4 | |a genomic profiling | |
| 650 | 4 | |a molecular genetic alterations | |
| 650 | 4 | |a next generation sequencing | |
| 650 | 4 | |a undifferentiated endometrial carcinoma | |
| 650 | 7 | |a Biomarkers, Tumor |2 NLM | |
| 650 | 7 | |a SMARCA4 protein, human |2 NLM | |
| 650 | 7 | |a EC 3.6.1.- |2 NLM | |
| 650 | 7 | |a DNA Helicases |2 NLM | |
| 650 | 7 | |a EC 3.6.4.- |2 NLM | |
| 650 | 7 | |a Nuclear Proteins |2 NLM | |
| 650 | 7 | |a Transcription Factors |2 NLM | |
| 700 | 1 | |a Busca, Aurelia |e verfasserin |4 aut | |
| 700 | 1 | |a Parra-Herran, Carlos |e verfasserin |4 aut | |
| 700 | 1 | |a Amemiya, Yutaka |e verfasserin |4 aut | |
| 700 | 1 | |a Nofech-Mozes, Sharon |e verfasserin |4 aut | |
| 700 | 1 | |a Djordjevic, Bojana |e verfasserin |4 aut | |
| 700 | 1 | |a Nucci, Marisa R |e verfasserin |4 aut | |
| 700 | 1 | |a Seth, Arun |e verfasserin |4 aut | |
| 700 | 1 | |a Mirkovic, Jelena |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Histopathology |d 1985 |g 83(2023), 3 vom: 01. Sept., Seite 366-375 |w (DE-627)NLM000284408 |x 0309-0167 |7 nnns |
| 773 | 1 | 8 | |g volume:83 |g year:2023 |g number:3 |g day:01 |g month:09 |g pages:366-375 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1111/his.14938 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 83 |j 2023 |e 3 |b 01 |c 09 |h 366-375 | ||