**4.3 Molecular pathology of ovarian endometrioid carcinomas**

OECs are characterised mainly by mutations in *PIK3CA* (15–40%), *ARID1A* (30–35%), a component of the SW1/SNF chromatin remodelling complex, *KRAS* (10–30%) and *CTNNB1* (25–60%) involved in the WNT/β-catenin signal transduction pathway [88–90]. Borderline endometrioid ovarian tumours have *CTNNB1* mutations in 90% of the cases [77, 90]. Other less common genomic alterations are mutations in *PTEN* (20–30%) with frequent loss of heterozygosity (45–75%), *TP53* (10–25%) and *POLE* (3–10%) [91, 92]. Somatic or germline predisposition mutations in MMR genes (MLH1, MSH2, MSH6, PMS2) can be found in 10–20% of the cases, some of them associated with Lynch syndrome [93, 94]. *POLE*-mutated EOCs and MMR-deficient ovarian endometrioid tumours have favourable clinical outcomes [95, 96]. *CTNNB1-*mutated tumours show low genomic complexity and are correlated with low-grade tumours and good prognosis, unlike their uterine endometrioid counterparts, which demonstrate worse clinical outcomes [77, 97]. *TP53* mutated EOCs have high genomic complexity with poor prognosis [98]. Synchronous presence of endometrial and ovarian endometrioid carcinomas can be encountered in 25% of the cases demonstrating a putative clonal relationship with favourable prognosis [99, 100]. Ovarian seromucinous carcinomas (mixed serous and endocervical-type mucinous carcinomas) are considered by the current WHO classification a subtype of endometrioid ovarian carcinomas based on their morphological and molecular overlapping features [5, 101, 102]. Based on their molecular features, EOCs are divided into four molecular subcategories: 1. *hypermutated* with microsatellite instability due to MMR deficiency (10–20%), 2. *ultramutated* due to *POLE* exonuclease domain mutations (3–10%), 3. *TP53 mutated* (10–25%) and 4. with *no specific molecular signatures* (60–70%) [95, 103]. Hypermutated and ultramutated EOCs display high mutation burden, a molecular finding that might be exploited for immunotherapeutic interventions. The genomic aberrations identified in EOCs might be used as targets for therapeutic interventions, such as targeting mutated *ARID1A* with HDAC inhibitors or targeting dysregulated MAPK or PI3K pathways using MEK or PIK3AC inhibitors, respectively [104, 105].
