Overview of Tumor Heterogeneity in High-Grade Serous Ovarian Cancers
Ovarian cancers encompass a group of neoplasms originating from germinal tissues and exhibiting distinct clinical, pathological, and molecular features. Among these, epithelial ovarian cancers (EOCs) are the most prevalent, comprising five distinct tumor histotypes. Notably, high-grade serous ovaria...
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MDPI AG
2023-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/20/15077 |
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| author | Eros Azzalini Giorgio Stanta Vincenzo Canzonieri Serena Bonin |
| author_facet | Eros Azzalini Giorgio Stanta Vincenzo Canzonieri Serena Bonin |
| author_sort | Eros Azzalini |
| collection | DOAJ |
| description | Ovarian cancers encompass a group of neoplasms originating from germinal tissues and exhibiting distinct clinical, pathological, and molecular features. Among these, epithelial ovarian cancers (EOCs) are the most prevalent, comprising five distinct tumor histotypes. Notably, high-grade serous ovarian cancers (HGSOCs) represent the majority, accounting for over 70% of EOC cases. Due to their silent and asymptomatic behavior, HGSOCs are generally diagnosed in advanced stages with an evolved and complex genomic state, characterized by high intratumor heterogeneity (ITH) due to chromosomal instability that distinguishes HGSOCs. Histologically, these cancers exhibit significant morphological diversity both within and between tumors. The histologic patterns associated with solid, endometrioid, and transitional (SET) and classic subtypes of HGSOCs offer prognostic insights and may indicate specific molecular profiles. The evolution of HGSOC from primary to metastasis is typically characterized by clonal ITH, involving shared or divergent mutations in neoplastic sub-clones within primary and metastatic sites. Disease progression and therapy resistance are also influenced by non-clonal ITH, related to interactions with the tumor microenvironment and further genomic changes. Notably, significant alterations occur in nonmalignant cells, including cancer-associated fibroblast and immune cells, during tumor progression. This review provides an overview of the complex nature of HGSOC, encompassing its various aspects of intratumor heterogeneity, histological patterns, and its dynamic evolution during progression and therapy resistance. |
| first_indexed | 2024-03-10T21:12:39Z |
| format | Article |
| id | doaj.art-4fa6c37f171f4cfe9266a9db6b4c35d0 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T21:12:39Z |
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| spelling | doaj.art-4fa6c37f171f4cfe9266a9db6b4c35d02023-11-19T16:41:15ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-10-0124201507710.3390/ijms242015077Overview of Tumor Heterogeneity in High-Grade Serous Ovarian CancersEros Azzalini0Giorgio Stanta1Vincenzo Canzonieri2Serena Bonin3Department of Medical Sciences (DSM), University of Trieste, 34149 Trieste, ItalyDepartment of Medical Sciences (DSM), University of Trieste, 34149 Trieste, ItalyDepartment of Medical Sciences (DSM), University of Trieste, 34149 Trieste, ItalyDepartment of Medical Sciences (DSM), University of Trieste, 34149 Trieste, ItalyOvarian cancers encompass a group of neoplasms originating from germinal tissues and exhibiting distinct clinical, pathological, and molecular features. Among these, epithelial ovarian cancers (EOCs) are the most prevalent, comprising five distinct tumor histotypes. Notably, high-grade serous ovarian cancers (HGSOCs) represent the majority, accounting for over 70% of EOC cases. Due to their silent and asymptomatic behavior, HGSOCs are generally diagnosed in advanced stages with an evolved and complex genomic state, characterized by high intratumor heterogeneity (ITH) due to chromosomal instability that distinguishes HGSOCs. Histologically, these cancers exhibit significant morphological diversity both within and between tumors. The histologic patterns associated with solid, endometrioid, and transitional (SET) and classic subtypes of HGSOCs offer prognostic insights and may indicate specific molecular profiles. The evolution of HGSOC from primary to metastasis is typically characterized by clonal ITH, involving shared or divergent mutations in neoplastic sub-clones within primary and metastatic sites. Disease progression and therapy resistance are also influenced by non-clonal ITH, related to interactions with the tumor microenvironment and further genomic changes. Notably, significant alterations occur in nonmalignant cells, including cancer-associated fibroblast and immune cells, during tumor progression. This review provides an overview of the complex nature of HGSOC, encompassing its various aspects of intratumor heterogeneity, histological patterns, and its dynamic evolution during progression and therapy resistance.https://www.mdpi.com/1422-0067/24/20/15077HGSOCintratumor heterogeneitySETclassicclonal evolutionTME |
| spellingShingle | Eros Azzalini Giorgio Stanta Vincenzo Canzonieri Serena Bonin Overview of Tumor Heterogeneity in High-Grade Serous Ovarian Cancers International Journal of Molecular Sciences HGSOC intratumor heterogeneity SET classic clonal evolution TME |
| title | Overview of Tumor Heterogeneity in High-Grade Serous Ovarian Cancers |
| title_full | Overview of Tumor Heterogeneity in High-Grade Serous Ovarian Cancers |
| title_fullStr | Overview of Tumor Heterogeneity in High-Grade Serous Ovarian Cancers |
| title_full_unstemmed | Overview of Tumor Heterogeneity in High-Grade Serous Ovarian Cancers |
| title_short | Overview of Tumor Heterogeneity in High-Grade Serous Ovarian Cancers |
| title_sort | overview of tumor heterogeneity in high grade serous ovarian cancers |
| topic | HGSOC intratumor heterogeneity SET classic clonal evolution TME |
| url | https://www.mdpi.com/1422-0067/24/20/15077 |
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