Abstract
Angiosarcoma is a malignant vascular endothelial neoplasm with various histological patterns. Despite its highly malignant potential, histological prognostic prediction has not been adopted for angiosarcoma. This study aimed to establish a method of predicting the prognosis of primary angiosarcoma. Formalin-fixed, paraffin-embedded samples from 104 primary angiosarcomas were prepared. All the cases were reviewed based on histological examinations with H&E staining. Because the French Fédération Nationale des Centres de Lutte Contre Le Cancer system (FNCLCC) is not adopted for angiosarcoma, we experimentally established a modified version of FNCLCC. Immunohistochemical staining for ERG, CD31, CD34, D2-40, HHV-8, p16, C-MYC, and p53 was performed. Fluorescence in situ hybridization (FISH) was performed for 31 cases to assay c-MYC gene amplification. Multivariate analysis revealed that age (> 70 years old) (p = 0.0011), non-cutaneous angiosarcoma (p = 0.0265), metastasis on diagnosis (p < 0.0001), size ≥ 5 cm (p = 0.0388), no taxane chemotherapy (p = 0.0388), strong nuclear atypia (p = 0.0087), and the presence of luminal structure in ≥ 50% of the tumor volume (p = 0.0009) were independent poor prognostic factors. Among angiosarcomas with luminal formation, mFNCLCC scores were significantly correlated with a poorer prognosis. The overexpression of p16 was associated with less luminal formation (p = 0.0192). Immunohistochemical analysis of C-MYC showed a moderate level of concordance with FISH (Kappa value = 0.45). This study suggested that luminal formation and nuclear atypia may be poor histological prognostic factors of angiosarcoma and that mFNCLCC would be useful for predicting the prognosis of angiosarcoma with luminal formation.
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Acknowledgements
The authors thank Masayuki Hirose and Junji Kishimoto (Center for Clinical and Translational Research at Kyushu University Hospital) for reviewing the statistical methods of this study.
This work was supported by JSPS KAKENHI Grant Number 19H03444.
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T. Ichiki performed the research and wrote the paper. Y. Yamada and T. Ito contributed to the research design and slide review. Y. Nakashima, M. Nakamura, T. Yoshizumi, A. Shiose, and K. Akashi contributed to the acquisition of the samples. T. Nakahara and Y. Oda designed the research and gave final approval of the manuscript. All authors critically reviewed and approved the manuscript.
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This study was conducted in accordance with the principles embodied in the Declaration of Helsinki. This study was also approved by the Ethics Committee of Kyushu University (Nos. 29-625, 29-429, 2020-361, 2021-165).
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Ichiki, T., Yamada, Y., Ito, T. et al. Histological and immunohistochemical prognostic factors of primary angiosarcoma. Virchows Arch 483, 59–69 (2023). https://doi.org/10.1007/s00428-023-03572-z
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DOI: https://doi.org/10.1007/s00428-023-03572-z