PIK3CA mutations and PI3K isoform expression define prognostic signatures in ovarian clear cell carcinoma.

Authors

Xiaonan Zhou, Yifei Liu, Jing Zhang, Min Ren, Gang Ji, Xu Cai, Rui Bi

Published in

Archives of gynecology and obstetrics. Jul 14, 2026. Epub Jul 14, 2026.

Abstract

Ovarian clear cell carcinoma (OCCC) is frequently characterized by dysregulation of the PI3K/AKT/mTOR (PAM) pathway; however, the expression patterns and clinical significance of class I PI3K catalytic isoforms remain incompletely understood. This study aimed to comprehensively evaluate PI3K catalytic subunit expression, co-expression patterns, and their prognostic relevance in OCCC.
A retrospective cohort of 100 patients with OCCC was analyzed. Immunohistochemistry was performed to assess the expression of p110α, p110β, p110δ, p110γ, and pAKT. PIK3CA exon 9 and exon 20 mutations were evaluated in available formalin-fixed paraffin-embedded tissues. Associations between PI3K isoforms, pAKT activation, clinicopathological characteristics, and survival outcomes were investigated.
The expression positivity rates of the four class I PI3K catalytic subunits in OCCC were 86% for p110γ, 77% for p110α, 58% for p110δ, and 56% for p110β. p110α and p110β were positively associated with pAKT activation, whereas p110δ and p110γ showed no significant association. p110δ expression was significantly correlated with PI3KCA exon9 mutation. Frequent co-expression of multiple PI3K catalytic subunits was observed, with simultaneous expression of all four isoforms representing the predominant pattern and significantly correlating with pAKT positivity. In advanced-stage disease, p110β expression was significantly associated with poorer progression-free survival (PFS), while pAKT positivity correlated with worse overall survival (OS) and PFS.
OCCC displays substantial heterogeneity in PI3K catalytic isoform expression and co-expression. p110α and p110β were associated with pAKT activation. In advanced-stage OCCC, high p110β expression was associated with poorer PFS, whereas pAKT activation was associated with both poorer PFS and OS, supporting further investigation of PI3K-targeted therapeutic strategies.

PMID:
42446738
Bibliographic data and abstract were imported from PubMed on 14 Jul 2026.

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