A High MCM6 Proliferative Index in Atypical Meningioma Is Associated with Shorter Progression Free and Overall Survivals
The aim of this study was to evaluate the prognostic value of MCM6, in comparison with Ki-67, in two series of grade 1 and 2 meningiomas, and to evaluate its correlation with methylation classes. The first cohort included 100 benign (grade 1, World Health Organization 2021) meningiomas, and the seco...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/2/535 |
| _version_ | 1797444759858446336 |
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| author | Guillaume Gauchotte Charles Bédel Emilie Lardenois Sébastien Hergalant Laura Cuglietta Robin Pflaum Stéphanie Lacomme Héloïse Pina Mathilde Treffel Fabien Rech Shyue-Fang Battaglia-Hsu |
| author_facet | Guillaume Gauchotte Charles Bédel Emilie Lardenois Sébastien Hergalant Laura Cuglietta Robin Pflaum Stéphanie Lacomme Héloïse Pina Mathilde Treffel Fabien Rech Shyue-Fang Battaglia-Hsu |
| author_sort | Guillaume Gauchotte |
| collection | DOAJ |
| description | The aim of this study was to evaluate the prognostic value of MCM6, in comparison with Ki-67, in two series of grade 1 and 2 meningiomas, and to evaluate its correlation with methylation classes. The first cohort included 100 benign (grade 1, World Health Organization 2021) meningiomas, and the second 69 atypical meningiomas (grade 2). Immunohistochemical Ki-67 and MCM6 labeling indices (LI) were evaluated independently by two observers. Among the atypical meningiomas, 33 cases were also studied by genome-wide DNA methylation. In grade 2 meningiomas, but not grade 1, both Ki-67 and MCM6 LIs were correlated with PFS (<i>p</i> = 0.004 and <i>p</i> = 0.005, respectively; Cox univariate analyses). Additionally, MCM6 was correlated with overall survival only in univariate analysis. In a multivariate model, including mitotic index, Ki-67, MCM6, age, sex, and the quality of surgical resection, only MCM6 was correlated with PFS (<i>p</i> = 0.046). Additionally, we found a significant correlation between PTEN loss and high MCM6 or Ki-67 LIs. Although no correlation was found with the methylation classes and subtypes returned by the meningioma algorithm MNGv2.4., MCM6 LI was significantly correlated with the methylation of 2 MCM6 gene body loci. In conclusion, MCM6 is a relevant prognostic marker in atypical meningiomas. This reproducible and easy-to-use marker allows the identification of a highly aggressive subtype of proliferative meningiomas, characterized notably by frequent PTEN losses, which was previously reported to be sensitive to histone deacetylase inhibitors. |
| first_indexed | 2024-03-09T13:16:10Z |
| format | Article |
| id | doaj.art-1e0de24dbda74909a72f1d9798a4a0b2 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T13:16:10Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-1e0de24dbda74909a72f1d9798a4a0b22023-11-30T21:35:15ZengMDPI AGCancers2072-66942023-01-0115253510.3390/cancers15020535A High MCM6 Proliferative Index in Atypical Meningioma Is Associated with Shorter Progression Free and Overall SurvivalsGuillaume Gauchotte0Charles Bédel1Emilie Lardenois2Sébastien Hergalant3Laura Cuglietta4Robin Pflaum5Stéphanie Lacomme6Héloïse Pina7Mathilde Treffel8Fabien Rech9Shyue-Fang Battaglia-Hsu10Department of Biopathology, CHRU Nancy, Université de Lorraine, F-54500 Vandoeuvre-lès-Nancy, FranceFaculty of Medicine, Université de Lorraine, F-54500 Vandoeuvre-lès-Nancy, FranceDepartment of Biopathology, CHRU Nancy, Université de Lorraine, F-54500 Vandoeuvre-lès-Nancy, FranceINSERM U1256, NGERE, F-54500 Vandoeuvre-lès-Nancy, FranceFaculty of Medicine, Université de Lorraine, F-54500 Vandoeuvre-lès-Nancy, FranceFaculty of Medicine, Université de Lorraine, F-54500 Vandoeuvre-lès-Nancy, FranceCentre de Ressources Biologiques, BB-0033-00035, CHRU Nancy, F-54500 Vandoeuvre-lès-Nancy, FranceFaculty of Medicine, Université de Lorraine, F-54500 Vandoeuvre-lès-Nancy, FranceDepartment of Biopathology, CHRU Nancy, Université de Lorraine, F-54500 Vandoeuvre-lès-Nancy, FranceCNRS, CRAN, Université de Lorraine, F-54000 Nancy, FranceCNRS, CRAN, Université de Lorraine, F-54000 Nancy, FranceThe aim of this study was to evaluate the prognostic value of MCM6, in comparison with Ki-67, in two series of grade 1 and 2 meningiomas, and to evaluate its correlation with methylation classes. The first cohort included 100 benign (grade 1, World Health Organization 2021) meningiomas, and the second 69 atypical meningiomas (grade 2). Immunohistochemical Ki-67 and MCM6 labeling indices (LI) were evaluated independently by two observers. Among the atypical meningiomas, 33 cases were also studied by genome-wide DNA methylation. In grade 2 meningiomas, but not grade 1, both Ki-67 and MCM6 LIs were correlated with PFS (<i>p</i> = 0.004 and <i>p</i> = 0.005, respectively; Cox univariate analyses). Additionally, MCM6 was correlated with overall survival only in univariate analysis. In a multivariate model, including mitotic index, Ki-67, MCM6, age, sex, and the quality of surgical resection, only MCM6 was correlated with PFS (<i>p</i> = 0.046). Additionally, we found a significant correlation between PTEN loss and high MCM6 or Ki-67 LIs. Although no correlation was found with the methylation classes and subtypes returned by the meningioma algorithm MNGv2.4., MCM6 LI was significantly correlated with the methylation of 2 MCM6 gene body loci. In conclusion, MCM6 is a relevant prognostic marker in atypical meningiomas. This reproducible and easy-to-use marker allows the identification of a highly aggressive subtype of proliferative meningiomas, characterized notably by frequent PTEN losses, which was previously reported to be sensitive to histone deacetylase inhibitors.https://www.mdpi.com/2072-6694/15/2/535MCM6Ki-67PTENproliferationatypical meningiomameningioma |
| spellingShingle | Guillaume Gauchotte Charles Bédel Emilie Lardenois Sébastien Hergalant Laura Cuglietta Robin Pflaum Stéphanie Lacomme Héloïse Pina Mathilde Treffel Fabien Rech Shyue-Fang Battaglia-Hsu A High MCM6 Proliferative Index in Atypical Meningioma Is Associated with Shorter Progression Free and Overall Survivals Cancers MCM6 Ki-67 PTEN proliferation atypical meningioma meningioma |
| title | A High MCM6 Proliferative Index in Atypical Meningioma Is Associated with Shorter Progression Free and Overall Survivals |
| title_full | A High MCM6 Proliferative Index in Atypical Meningioma Is Associated with Shorter Progression Free and Overall Survivals |
| title_fullStr | A High MCM6 Proliferative Index in Atypical Meningioma Is Associated with Shorter Progression Free and Overall Survivals |
| title_full_unstemmed | A High MCM6 Proliferative Index in Atypical Meningioma Is Associated with Shorter Progression Free and Overall Survivals |
| title_short | A High MCM6 Proliferative Index in Atypical Meningioma Is Associated with Shorter Progression Free and Overall Survivals |
| title_sort | high mcm6 proliferative index in atypical meningioma is associated with shorter progression free and overall survivals |
| topic | MCM6 Ki-67 PTEN proliferation atypical meningioma meningioma |
| url | https://www.mdpi.com/2072-6694/15/2/535 |
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