Validation of a one-step genomics-based molecular classifier for endometrial carcinoma in a large Chinese population
Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved..
OBJECTIVE: The aim of this study is to delineate the molecular classification features within Chinese endometrial cancer (EC) patients and to evaluate the concurrence between two widely employed methods for diagnosing EC molecular subtypes.
METHODS: This retrospective observational cohort study encompassed 479 cases of EC for analysis. Utilizing next-generation sequencing (NGS) panels targeting POLE, TP53, and microsatellite instability (MSI) status, four subtypes [POLE ultramutated (POLE mut), MMR-deficient (MMRd), p53 abnormal (p53abn), and no specific molecular profile (NSMP)] were classified. Immunohistochemistry (IHC) was employed to ascertain the expression of p53 and MMR proteins.
RESULTS: Among the 479 patients, the distribution of EC subtypes was as follows: 28 (5.85%) POLE mut, 67 (13.99%) MMRd, 60 (12.53%) p53abn, and 324 (67.64%) NSMP. When compared to published findings on EC subtypes in the Caucasian population, our real-world data on Chinese ECs revealed a notably higher proportion of NSMP/CNL (copy number low). The evaluation of MSI/MMR status through NGS-based and IHC-based methods displayed substantial concordance (Kappa = 0.91). Slight discordance between the two techniques in identifying p53 abnormalities (Kappa = 0.83) might stem from TP53 truncating mutations, cytoplasmic p53 expression, null TP53 mutants, and well-documented challenges in interpreting p53 IHC.
CONCLUSIONS: Chinese ECs exhibit distinctive molecular attributes. For accurate molecular subtyping of Chinese ECs, additional molecular markers that align with the Chinese population's characteristics should be incorporated into existing classifiers. The study's outcomes underscore a strong agreement between NGS and IHC in TP53/p53 detection and MSI assessment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:254 |
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| Enthalten in: |
Pathology, research and practice - 254(2024) vom: 09. Feb., Seite 155152 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kang, Nan [VerfasserIn] |
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| Links: |
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| Themen: |
DNA Polymerase II |
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| Anmerkungen: |
Date Completed 14.02.2024 Date Revised 14.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.prp.2024.155152 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM367681536 |
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| 100 | 1 | |a Kang, Nan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Validation of a one-step genomics-based molecular classifier for endometrial carcinoma in a large Chinese population |
| 264 | 1 | |c 2024 | |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved. | ||
| 520 | |a OBJECTIVE: The aim of this study is to delineate the molecular classification features within Chinese endometrial cancer (EC) patients and to evaluate the concurrence between two widely employed methods for diagnosing EC molecular subtypes | ||
| 520 | |a METHODS: This retrospective observational cohort study encompassed 479 cases of EC for analysis. Utilizing next-generation sequencing (NGS) panels targeting POLE, TP53, and microsatellite instability (MSI) status, four subtypes [POLE ultramutated (POLE mut), MMR-deficient (MMRd), p53 abnormal (p53abn), and no specific molecular profile (NSMP)] were classified. Immunohistochemistry (IHC) was employed to ascertain the expression of p53 and MMR proteins | ||
| 520 | |a RESULTS: Among the 479 patients, the distribution of EC subtypes was as follows: 28 (5.85%) POLE mut, 67 (13.99%) MMRd, 60 (12.53%) p53abn, and 324 (67.64%) NSMP. When compared to published findings on EC subtypes in the Caucasian population, our real-world data on Chinese ECs revealed a notably higher proportion of NSMP/CNL (copy number low). The evaluation of MSI/MMR status through NGS-based and IHC-based methods displayed substantial concordance (Kappa = 0.91). Slight discordance between the two techniques in identifying p53 abnormalities (Kappa = 0.83) might stem from TP53 truncating mutations, cytoplasmic p53 expression, null TP53 mutants, and well-documented challenges in interpreting p53 IHC | ||
| 520 | |a CONCLUSIONS: Chinese ECs exhibit distinctive molecular attributes. For accurate molecular subtyping of Chinese ECs, additional molecular markers that align with the Chinese population's characteristics should be incorporated into existing classifiers. The study's outcomes underscore a strong agreement between NGS and IHC in TP53/p53 detection and MSI assessment | ||
| 650 | 4 | |a Observational Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Endometrial cancer | |
| 650 | 4 | |a IHC | |
| 650 | 4 | |a Molecular classification | |
| 650 | 4 | |a NGS | |
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| 700 | 1 | |a Zhang, Xiaobo |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zhiqi |e verfasserin |4 aut | |
| 700 | 1 | |a Dai, Yibo |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Shanshan |e verfasserin |4 aut | |
| 700 | 1 | |a Su, Wenqing |e verfasserin |4 aut | |
| 700 | 1 | |a Gai, Fei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Changbin |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Danhua |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jianliu |e verfasserin |4 aut | |
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