Unique Molecular Features in High-Risk Histology Endometrial Cancers
Abstract
:1. Introduction
2. Biologic Differences in Low- And High-Risk Histologic Endometrial Carcinomas
2.1. Clinical Features of Low- and High-Risk Histologic Carcinomas
2.2. Health Disparities and High-Risk Histologic Carcinomas
2.3. Pre-Cursor Lesions
2.4. Stem Cells and Stem-Cell Markers
2.5. Unique Molecular Features
3. Treatment
3.1. Primary Surgical Therapy
3.2. Adjuvant Treatment
3.3. Hormone Therapy
3.4. Targeted Therapy for HER2+ Tumors
3.5. Immune Therapy for MSI-H Carcinomas
3.6. Select Studies from Promising Molecular Targeted Therapies
4. Model Systems
4.1. Mouse Models
4.2. In Vitro Systems
5. Future Systems
6. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Characteristic | Low-Risk Histology (85%) | High-Risk Histology (15%) |
---|---|---|
Characteristic histology | Low-grade endometrioid | • Uterine carcinosarcoma • High-grade endometrioid • High-grade clear cell • High-grade serous |
5-year survival | 83% | 44% |
Primary therapy | • Removal of uterus and ovaries | • Removal of uterus and ovaries |
• Obesity may limit surgical options | • Aggressive tumor debulking | |
• Fertility preservation with progesterone IUD | ||
Adjuvant therapy | Usually none | Chemotherapy+/-radiotherapy |
Timing of presentation | • Young women (Lynch) | • Postmenopausal |
• Peri-menopausal | ||
• Postmenopausal | ||
Precursor lesion | • Proliferative endometrium | • Atrophic endometrium |
• Endometrial hyperplasia |
Marker | Low-Grade Endometrioid | High-Grade Endometrioid | Clear Cell | Serous | Uterine Carcinosarcoma | References |
---|---|---|---|---|---|---|
ARID1A- | 8% | 33–46% | 13–22% | 0–9% | 7% | [12,44,45,46] |
Estrogen receptor+ | 84–96% | 31–82% | 9–21% | 31–54% | 8–36% | [12,44,47,48,49,50,51,52] |
HNF1β+ | 39% | 5% | 67–83% | 22% | [44,45] | |
Napsin A+ | 0% | 0% | 70–88% | 8% | 0% | [44,47,53] |
p16+ | 1–7% | 11–25% | 45–80% | 80–100% | 60–78% | [12,47,48,49,51] |
p53+ | 3–18% | 18–69% | 22–25% | 44–94% | 26–80% | [12,46,48,50,52,54,55] |
Progesterone receptor+ | 83–100% | 42–68% | 11–45% | 6–54% | 0–42% | [12,44,47,48,49,51,52,55] |
PTEN- | 53% | 28–75% | 33% | 6–100% | 39% | [12,48,52] |
Vimentin+ | 88–90% | 77–92% | 38–91% | 27–83% | 100% | [12,45,51] |
WT1+ | 0–3% | 0–27% | 0–50% | 33–63% | 70% | [12,54,56] |
Genetic Change | Low-Grade Endometrioid | High-Grade Endometrioid | Clear Cell | Serous | Uterine Carcinosarcoma | Reference |
---|---|---|---|---|---|---|
ARID1A mutation | 46.7% | 60% | 14–22% | 8–10.8% | 12–23.8% | [15,58,60,61] |
CTNNB1 mutation | 23.8% | 20% | 0% | 1–2.7% | 2–4.8% | [60,61,62] |
KRAS mutation | 15–24% | 26.7% | 0–13% | 3–8.1% | 9–29% | [15,60,61] |
PIK3CA mutation | 38–56% | 56.7% | 14–37% | 17–43% | 15–41% | [8,15,58,60] |
PTEN mutation | 67–80% | 90% | 0–25% | 2.7–10% | 18–47% | [15,60,61] |
TP53 mutation | 10% | 30% | 31–50% | > 85% | 64–91% | [8,15,60] |
Microsatellite instability | 30% | 56% | 0–19% | 0% | 3.5–21% | [15,58,62,63] |
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Pandita, P.; Wang, X.; Jones, D.E.; Collins, K.; Hawkins, S.M. Unique Molecular Features in High-Risk Histology Endometrial Cancers. Cancers 2019, 11, 1665. https://doi.org/10.3390/cancers11111665
Pandita P, Wang X, Jones DE, Collins K, Hawkins SM. Unique Molecular Features in High-Risk Histology Endometrial Cancers. Cancers. 2019; 11(11):1665. https://doi.org/10.3390/cancers11111665
Chicago/Turabian StylePandita, Pooja, Xiyin Wang, Devin E. Jones, Kaitlyn Collins, and Shannon M. Hawkins. 2019. "Unique Molecular Features in High-Risk Histology Endometrial Cancers" Cancers 11, no. 11: 1665. https://doi.org/10.3390/cancers11111665