Atypical Mitotic Figures Are Prognostically Meaningful for Canine Cutaneous Mast Cell Tumors
Cell division through mitosis (microscopically visible as mitotic figures, MFs) is a highly regulated process. However, neoplastic cells may exhibit errors in chromosome segregation (microscopically visible as atypical mitotic figures, AMFs) resulting in aberrant chromosome structures. AMFs have bee...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | Veterinary Sciences |
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| Online Access: | https://www.mdpi.com/2306-7381/11/1/5 |
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| author | Christof A. Bertram Alexander Bartel Taryn A. Donovan Matti Kiupel |
| author_facet | Christof A. Bertram Alexander Bartel Taryn A. Donovan Matti Kiupel |
| author_sort | Christof A. Bertram |
| collection | DOAJ |
| description | Cell division through mitosis (microscopically visible as mitotic figures, MFs) is a highly regulated process. However, neoplastic cells may exhibit errors in chromosome segregation (microscopically visible as atypical mitotic figures, AMFs) resulting in aberrant chromosome structures. AMFs have been shown to be of prognostic relevance for some neoplasms in humans but not in animals. In this study, the prognostic relevance of AMFs was evaluated for canine cutaneous mast cell tumors (ccMCT). Histological examination was conducted by one pathologist in whole slide images of 96 cases of ccMCT with a known survival time. Tumor-related death occurred in 11/18 high-grade and 2/78 low-grade cases (2011 two-tier system). The area under the curve (AUC) was 0.859 for the AMF count and 0.880 for the AMF to MF ratio with regard to tumor-related mortality. In comparison, the AUC for the mitotic count was 0.885. Based on our data, a prognostically meaningful threshold of ≥3 per 2.37 mm<sup>2</sup> for the AMF count (sensitivity: 76.9%, specificity: 98.8%) and >7.5% for the AMF:MF ratio (sensitivity: 76.9%, specificity: 100%) is suggested. While the mitotic count of ≥ 6 resulted in six false positive cases, these could be eliminated when combined with the AMF to MF ratio. In conclusion, the results of this study suggests that AMF enumeration is a prognostically valuable test, particularly due to its high specificity with regard to tumor-related mortality. Additional validation and reproducibility studies are needed to further evaluate AMFs as a prognostic criterion for ccMCT and other tumor types. |
| first_indexed | 2024-03-08T10:33:31Z |
| format | Article |
| id | doaj.art-806adbe559164d3eb3a53b5faa08334f |
| institution | Directory Open Access Journal |
| issn | 2306-7381 |
| language | English |
| last_indexed | 2024-03-08T10:33:31Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Veterinary Sciences |
| spelling | doaj.art-806adbe559164d3eb3a53b5faa08334f2024-01-26T18:45:06ZengMDPI AGVeterinary Sciences2306-73812023-12-01111510.3390/vetsci11010005Atypical Mitotic Figures Are Prognostically Meaningful for Canine Cutaneous Mast Cell TumorsChristof A. Bertram0Alexander Bartel1Taryn A. Donovan2Matti Kiupel3Institute of Veterinary Pathology, University of Veterinary Medicine Vienna, 1210 Vienna, AustriaInstitute for Veterinary Epidemiology and Biostatistics, Freie Universität Berlin, 14163 Berlin, GermanyDepartment of Anatomic Pathology, The Schwarzman Animal Medical Center, New York, NY 10065, USAVeterinary Diagnostic Laboratory, Michigan State University, Lansing, MI 48910, USACell division through mitosis (microscopically visible as mitotic figures, MFs) is a highly regulated process. However, neoplastic cells may exhibit errors in chromosome segregation (microscopically visible as atypical mitotic figures, AMFs) resulting in aberrant chromosome structures. AMFs have been shown to be of prognostic relevance for some neoplasms in humans but not in animals. In this study, the prognostic relevance of AMFs was evaluated for canine cutaneous mast cell tumors (ccMCT). Histological examination was conducted by one pathologist in whole slide images of 96 cases of ccMCT with a known survival time. Tumor-related death occurred in 11/18 high-grade and 2/78 low-grade cases (2011 two-tier system). The area under the curve (AUC) was 0.859 for the AMF count and 0.880 for the AMF to MF ratio with regard to tumor-related mortality. In comparison, the AUC for the mitotic count was 0.885. Based on our data, a prognostically meaningful threshold of ≥3 per 2.37 mm<sup>2</sup> for the AMF count (sensitivity: 76.9%, specificity: 98.8%) and >7.5% for the AMF:MF ratio (sensitivity: 76.9%, specificity: 100%) is suggested. While the mitotic count of ≥ 6 resulted in six false positive cases, these could be eliminated when combined with the AMF to MF ratio. In conclusion, the results of this study suggests that AMF enumeration is a prognostically valuable test, particularly due to its high specificity with regard to tumor-related mortality. Additional validation and reproducibility studies are needed to further evaluate AMFs as a prognostic criterion for ccMCT and other tumor types.https://www.mdpi.com/2306-7381/11/1/5atypical mitotic figurecell divisiondigital microscopydogmitotic countmast cell tumor |
| spellingShingle | Christof A. Bertram Alexander Bartel Taryn A. Donovan Matti Kiupel Atypical Mitotic Figures Are Prognostically Meaningful for Canine Cutaneous Mast Cell Tumors Veterinary Sciences atypical mitotic figure cell division digital microscopy dog mitotic count mast cell tumor |
| title | Atypical Mitotic Figures Are Prognostically Meaningful for Canine Cutaneous Mast Cell Tumors |
| title_full | Atypical Mitotic Figures Are Prognostically Meaningful for Canine Cutaneous Mast Cell Tumors |
| title_fullStr | Atypical Mitotic Figures Are Prognostically Meaningful for Canine Cutaneous Mast Cell Tumors |
| title_full_unstemmed | Atypical Mitotic Figures Are Prognostically Meaningful for Canine Cutaneous Mast Cell Tumors |
| title_short | Atypical Mitotic Figures Are Prognostically Meaningful for Canine Cutaneous Mast Cell Tumors |
| title_sort | atypical mitotic figures are prognostically meaningful for canine cutaneous mast cell tumors |
| topic | atypical mitotic figure cell division digital microscopy dog mitotic count mast cell tumor |
| url | https://www.mdpi.com/2306-7381/11/1/5 |
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