Table 1.
Summary of genetic alterations and microenvironmental characteristics by ovarian cancer subtype.
| OC subtype | Precent of EOC | Genetic alterations | Microenvironment | References |
|---|---|---|---|---|
| HGSC | 75% | TP53, BRCA1, BRCA2, BRIP1, RAD51C, RAD51D, STK11 | CAFs and TAMs enriched. Immunosuppressive. Often high levels of VEGF. High levels of CD8+ TILs. | (2, 54, 67–71) |
| LGSC | 5% |
KRAS, NRAS, BRAF, USP9X, MACF1, ARID1A, NF2, DOT1L, ASH1L |
Lower levels of TAMs and PD-L1 than HGSC. Higher levels FAP+ CAFs and STING than HGSC. | (45, 60, 72–76) |
| Endometrioid OC | 10-20% |
PTEN, CTNNB1 (β-catenin), PIK3CA, ARID1A |
Lower level of TAMs, CAFs, T-cells (exhausted and total), PD-L1, and TGF-β than HGSC. Higher levels of CD44 and B7-H3 compared to other subtypes. | (54, 77–82) |
| Mucinous OC | 3-5% |
KRAS, TP53, PIK3CA, CDKN2A, ERBB2, BRAF, SMAD4, SRC, CTNNB1 (β-catenin), FGR2, STK11 |
Similar level of TAMs and PD-L1 as HGSC. Higher levels of CTLA-4 compared to HGSC. Higher levels of SMA, FAP+ CAFs, and Tregs compared to other subtypes. | (54, 82–85) |
| CCOC | 5-11% | ARID1A, PIK3CA, TET2, TSC1, BRCA2, GNAS, SMAD4, MYC, NTRK1, KRAS | Lower level of TAMs than HGSC. Similar levels of PD-L1 to HGSC. High levels of MET and phospho-PRAS40 proteins than HGSC. | (54, 79, 80, 82, 86–89) |
| DDOC | 2% |
SWI/SNF (BRG1 or IN11), ARID1A/ARID1B, SMARCA4, SMARCB1 |
Mostly unknown. | (90–92) |
Ovarian cancer (OC) subtypes with alteration and microenvironment features from the literature. Genetic alterations in bold indicate the most frequent for that subtype. Microenvironment features are compared to HGSC or other subtypes. Increased levels, decreased levels, and similar levels in comparison are indicated with green, red, and blue, respectively. EOC, epithelial ovarian cancer. HGSC, high-grade serous ovarian cancer. LGSC, low-grade serous ovarian cancer. CCOC, clear cell ovarian carcinoma. DDOC, dedifferentiated ovarian carcinoma. CAFs, cancer associated fibroblasts. TAMs, tumor associated macrophages. VEGF, vascular endothelial growth factor. TILs, tumor-infiltrating lymphocytes. Tregs, regulatory T-cells. FAP, fibroblast activation protein. MET, mesenchymal-epithelial transition.