Table 3.
Recommendations for biomarker testing in ovarian cancer
| Biomarker category | Specific test | Recommendation level | Clinical application | |
|---|---|---|---|---|
| Histopathological classification | ||||
| General approach | Histologic examination + selective IHC/molecular testing | Mandatory | Diagnostic classification; use ancillary techniques for challenging or overlapping morphologies | |
| High-grade serous carcinoma | ||||
| General approach | p53, WT1, PAX8, ER (IHC) | Optional | Diagnostic confirmation when morphology is non-classic | |
| HRD testing | Mandatory | At diagnosis for stages III–IV to guide PARP inhibitor therapy | ||
| Endometrioid carcinoma | ||||
| General approach | ER, PR, PAX8, CK7, WT1 (IHC) | Optional | Diagnostic confirmation when needed | |
| Molecular subgrouping (POLE, MMR, TP53, NSMP) | Optional | Prognostic stratification and treatment selection | ||
| HRD testing | Mandatory | At diagnosis, if high grade, for stages III–IV | ||
| Clear cell carcinoma | ||||
| General approach | Napsin A, HNF-1β, PAX8 (IHC) | Optional | Diagnostic confirmation | |
| ARID1A (IHC) | Optional | Loss supports diagnosis and identifies potential therapeutic targets | ||
| MSI/MMR testing | Optional | Identifies immunotherapy candidates | ||
| HRD testing | Mandatory | At diagnosis for stages III–IV | ||
| Low-grade serous carcinoma | ||||
| General approach | WT1, ER, p53 (IHC) | Optional | Distinguish from HGSOC when needed | |
| MAPK pathway mutations (KRAS, BRAF, NRAS) | Investigational | May guide targeted therapy in clinical trials | ||
| Mucinous carcinoma | ||||
| General approach | CK7, CK20, CDX2, PAX8, WT1 (IHC) | Optional | Differentiate primary from metastatic disease | |
| HER2 amplification | Optional | Prognostic and potential therapeutic value | ||
| KRAS mutations | Optional | Prognostic and potential therapeutic value | ||
| Other rare carcinomas | ||||
| General approach | Extended IHC panel (GATA3, TTF-1, CD10, MMR) | Optional | Subtype classification | |
| HRD testing | Mandatory | At diagnosis for stages III–IV | ||
| Serum biomarkers | ||||
| CA-125 | Serum measurement | Mandatory | Treatment monitoring and relapse detection (GCIG criteria); NOT for population screening | |
| HE4 | Serum measurement | Optional | Combined with CA-125 to improve diagnostic specificity, especially in premenopausal women | |
| Multivariate indices (RMI, OVA1, ROMA) | Algorithmic tools | Optional | Differentiate benign from malignant adnexal masses when ultrasound is inconclusive | |
| Treatment response | ||||
| Chemotherapy Response Score (CRS) | Histologic assessment | Mandatory | Evaluate omental specimens post-neoadjuvant chemotherapy in HGSOC; CRS3 predicts improved PFS/OS | |
| CA-125 elimination kinetics (KELIM) | Calculated parameter | Optional | Predictive marker for treatment response | |
| Molecular biomarkers | ||||
| HRD status | NGS-based assays | Mandatory | At diagnosis for all high-grade non-mucinous carcinomas, stages III–IV; requires ≥ 30% tumor cellularity; guides PARP inhibitor maintenance | |
| BRCA1/2 (somatic) | NGS or targeted sequencing | Mandatory | Prognostic and predictive value; if positive, perform germline testing | |
| BRCA1/2 (germline) | Genetic testing | Mandatory | When somatic mutation detected or family history suggests hereditary syndrome | |
| TP53/p53 | IHC | Mandatory | Confirm HGSOC diagnosis; molecular subgrouping in endometrioid carcinoma | |
| Folate receptor-α (FRα) | IHC (validated assay) | Optional | Identify candidates for mirvetuximab soravtansine (requires ≥ 75% cells with moderate/strong staining) | |
| HRR genes (RAD51C/D, PALB2, BRIP1, ATM) | NGS | Optional | If mutation detected, perform germline testing | |
| HER2 | IHC/FISH | Optional | In high-grade tumors for clinical trial eligibility or HER2-targeted therapy (e.g., trastuzumab deruxtecan) | |
| MMR/MSI | IHC (MLH1, PMS2, MSH2, MSH6) + MLH1 methylation | Optional | Identifies immunotherapy candidates (MSI-H/MMRd); consider in clear cell and endometrioid carcinomas | |
| CCNE1 amplification | IHC/FISH/NGS | Investigational | Poor PARP inhibitor response; may guide WEE1 inhibitor trials | |
| ARID1A | IHC | Optional | Loss supports diagnosis in clear cell/endometrioid carcinomas; identifies potential therapeutic targets | |
| Emerging biomarkers | ||||
| Cadherin-6 (CDH6) | IHC | Investigational | For ADC trial eligibility (e.g., raludotatug deruxtecan); ≥ 1 + staining required | |
| TROP-2 | IHC | Investigational | Guide enrollment in ADC trials (Dato-DXd, DB-1305, Sat-TMT) | |
| RAD51 foci | Functional assay | Investigational | Potential HRD surrogate; validation ongoing | |