Combined genomic and molecular analysis defines prognostic markers of relapse in stage IA-IC1 clear cell ovarian carcinoma.

OBJECTIVE

Clear cell ovarian carcinoma (CCOC) is generally associated with a favourable prognosis, however up to 30 % of low-stage cases relapse within five years. The benefit of adjuvant chemotherapy in early-stage disease (FIGO IA-IC1) remains uncertain. This study aimed to identify molecular and immune markers associated with relapse in a well-characterized CCOC cohort.

METHODS

We analyzed 85 CCOC cases identified through the Edinburgh Ovarian Cancer Database. Targeted DNA sequencing assessed genomic alterations, while CD3 and CD8 immunohistochemistry evaluated tumour immune infiltration. Tumours were stratified by stage (IA-IC1, IC2-II, III-IV), and progression-free survival (PFS) analysis included stage, age, genomic features, and immune markers.

RESULTS

Common genomic alterations included ARID1A (49 %) and PIK3CA (42 %) mutations, PIK3-AKT pathway perturbations (60 %), and mismatch repair-related mutational signatures (25.9 %). Genomic features were not significantly associated with tumour stage; however, low-stage tumours (IA-IC1) were enriched in CD3+ (40 % cases) and CD8+ (29 % cases) tumour-infiltrating lymphocytes (TILs) compared to higher-stage tumours (IC2-II: 13 %/7 %; III-IV: 9 %/0 %). In univariate analysis, low CD3+ TIL levels were significantly associated with reduced PFS (HR = 4.4, P = 0.042), and ARID1A wild-type status was linked to poorer PFS in low-stage tumours (HR = 7.2, P = 0.088). Notably, the combination of ARID1A wild-type status and CD3+ TIL depletion identified a high-risk subgroup with increased relapse risk (HR = 11.7, P = 0.051).

CONCLUSIONS

The combination of ARID1A wild-type status and low CD3+ TIL levels suggests higher relapse risk in low-stage CCOC. These findings warrant further investigation into targeted and immune-based therapies for high-risk early-stage patients.