| Pathway / Function Group | Gene / Pathway | Type of Alteration in Ovarian Endometrioid Carcinoma | Frequency / Enrichment | Functional Impact | Clinical Significance | Associated Molecular Subtype |
|---|---|---|---|---|---|---|
| Chromatin remodeling | **ARID1A** | Predominantly loss-of-function alterations; often reflected by loss of protein expression | Recurrent/frequent; shared with endometriosis-associated tumors and often co-occurs with **PIK3CA** alterations (pqac-00000002, pqac-00000006) | Disrupts SWI/SNF chromatin remodeling, altering transcriptional control and differentiation programs | Supports endometriosis-associated pathogenesis; candidate biomarker for synthetic-lethality and epigenetic strategies; useful in molecular profiling (pqac-00000006) | Most often **NSMP** or **MMRd** backgrounds; can occur across subtypes |
| PI3K/AKT/mTOR signaling | **PIK3CA** | Activating/gain-of-function mutation | Recurrent/frequent; commonly co-occurs with **ARID1A** and present in endometriosis-related precursor lesions (pqac-00000006) | Activates PI3K/AKT/mTOR signaling, promoting proliferation, survival, metabolism, and therapy resistance | Suggests actionable pathway dependence; rationale for PI3K/AKT/mTOR-targeted therapy development (pqac-00000006) | Most often **NSMP**; also seen in **MMRd** tumors |
| PI3K/AKT/mTOR signaling | **PTEN** | Inactivating mutation/loss of function; sometimes loss of expression | Recurrent/frequent in OEC; highlighted as characteristic of endometrioid tumors (pqac-00000002, pqac-00000006) | Releases inhibition of PI3K signaling, increasing AKT/mTOR pathway activation | Supports endometriosis-to-carcinoma progression model; may inform targeted pathway inhibition strategies (pqac-00000006) | Most often **NSMP**; also present in **MMRd** |
| Wnt / cell fate | **CTNNB1** | Activating mutation / β-catenin pathway alteration | Characteristic/recurrent in OEC (pqac-00000002, pqac-00000006) | Activates Wnt/β-catenin signaling, affecting epithelial differentiation, proliferation, and glandular/squamous morphology | Helpful lineage-defining alteration for endometrioid histotype; may aid distinction from other ovarian carcinoma types (pqac-00000002) | Most commonly **NSMP** |
| MAPK signaling | **KRAS** | Activating mutation | Less common than PTEN/PIK3CA/CTNNB1 but recurrent; also seen in benign endometriotic lesions (pqac-00000006) | Activates MAPK signaling, supporting growth and clonal evolution from precursor lesions | Supports precursor-lesion model and molecular heterogeneity; potential entry point for pathway-based trials in selected tumors | Usually **NSMP** |
| DNA mismatch repair | **MLH1** | Loss of protein expression from mutation or promoter hypermethylation | Present in the **MMRd** subset; sporadic cases often involve promoter hypermethylation (pqac-00000006) | Causes mismatch-repair deficiency, hypermutation, and microsatellite instability | Important for Lynch syndrome triage when unmethylated; predicts eligibility/relevance for immune checkpoint blockade in MMRd disease (pqac-00000001, pqac-00000006) | **MMRd** |
| DNA mismatch repair | **MSH2** | Loss-of-function germline or somatic alteration with loss of protein expression | Enriched in Lynch-associated OEC within the MMRd subset (pqac-00000001) | Defective mismatch repair leading to MSI and increased neoantigen load | Strong Lynch syndrome implication; triggers genetic counseling and germline testing; may predict immunotherapy sensitivity (pqac-00000001) | **MMRd** |
| DNA mismatch repair | **MSH6** | Loss-of-function germline or somatic alteration with loss of protein expression | Enriched in Lynch-associated OEC within the MMRd subset (pqac-00000001) | Defective mismatch repair with hypermutator phenotype | Supports Lynch syndrome diagnosis and ICI consideration; should be included in routine MMR IHC panels (pqac-00000001) | **MMRd** |
| DNA mismatch repair | **PMS2** | Loss-of-function germline or somatic alteration with loss of protein expression | Present in MMRd tumors, either isolated or paired with MLH1 loss depending on mechanism (pqac-00000001) | Defective mismatch repair and MSI development | Lynch screening relevance; contributes to molecular classification and therapeutic stratification (pqac-00000001) | **MMRd** |
| Replication proofreading | **POLE** | Pathogenic exonuclease-domain mutation causing ultramutation | Uncommon but clinically important subset; specifically recognized in OEC molecular classification (pqac-00000001, pqac-00000003) | Causes defective proofreading during DNA replication, producing ultrahigh tumor mutational burden | Associated with excellent prognosis; may justify treatment de-escalation in some contexts and may enhance immunotherapy responsiveness (pqac-00000001) | **POLE-ultramutated** |
| Genome stability / TP53 axis | **p53 pathway** | Abnormal p53 pattern / TP53 alteration in a minority, especially high-grade cases | Minority subset; defines biologically aggressive p53-abnormal OECs (pqac-00000001, pqac-00000003) | Genomic instability and more aggressive tumor biology | Associated with poorer prognosis and need for intensified management relative to POLEmut/MMRd subsets (pqac-00000001) | **p53-abnormal** |
| Integrated molecular classification | **MMR pathway (overall)** | Deficiency detected by IHC/MSI testing rather than a single-gene event | Clinically meaningful subset; OEC is enriched for Lynch-associated tumors, supporting routine MMR testing (pqac-00000001, pqac-00000003) | Hypermutation, MSI, immune activation potential | Essential for universal screening workflows, prognostic stratification, and selection for checkpoint inhibition (pqac-00000001) | **MMRd** |
| Integrated molecular classification | **PI3K/AKT/mTOR pathway (overall)** | Combined activation through **PIK3CA** gain and/or **PTEN** loss | One of the dominant pathway-level themes in OEC and endometriosis-associated ovarian cancer (pqac-00000006) | Promotes survival, proliferation, metabolic rewiring, and progression from endometriosis | Major translational target class; links precursor lesions to invasive carcinoma (pqac-00000006) | Mostly **NSMP**, also across other subtypes |
| Integrated molecular classification | **Wnt/β-catenin pathway (overall)** | Pathway activation mainly through **CTNNB1** alteration | Characteristic of endometrioid differentiation (pqac-00000002, pqac-00000006) | Reinforces endometrioid lineage program and tumor growth | Useful for histotype assignment and biologic interpretation of morphology | Mostly **NSMP** |


*Table: This table summarizes the major recurrent molecular alterations and pathway-level abnormalities reported in ovarian endometrioid carcinoma, including their biologic effects and clinical implications. It is useful for linking histology, molecular subtype, prognosis, and potential therapeutic opportunities.*