Molecular subtype of ovarian clear cell carcinoma: an analysis of 80 Chinese patients using the TCGA molecular classification of endometrial cancer

BMC Cancer. 2025 Jan 15;25(1):90. doi: 10.1186/s12885-024-13389-x.

Abstract

Background: To assess the utility of the TCGA molecular classification of endometrial cancer in a well-annotated, moderately sized, consecutive cohort of Chinese patients with ovarian clear cell carcinoma (OCCC).

Methods: We performed DNA sequencing on 80 OCCC patients via a panel that contains 520 cancer-related genes. The TCGA molecular subtyping method was utilized for classification. The clinicopathological features were analysed, and the survival correlation was assessed for each subtype.

Results: The most common mutated genes were ARID1A (49%) and PIK3CA (48%). No pathogenic POLE mutations were detected. MSI-high (MSI-H) tumours were observed in 5 (6.3%) patients. A total of 16.3% (13/80) of the patients were classified as the p53 abnormal (p53abn) subtype, and 77.5% (62/80) were classified as the nonspecific molecular profile (NSMP) subtype. All the MSI-H patients had ARID1A mutations, whereas patients with the p53abn subtype had the lowest percentage of ARID1A mutations (27.3%). No significant differences were observed between the molecular subtypes and clinicopathological features. The progression-free survival and overall survival of the entire cohort were closely associated with FIGO stage (p < 0.01), the presence of residual tumour (p < 0.01), and the platinum response (p < 0.01). Molecular classification did not significantly impact prognosis. Univariate analysis revealed that TP53 mutations in advanced-stage (FIGO III-IV) patients were associated with shorter survival.

Conclusions: We did not find prognostic significance of TCGA molecular subtyping in OCCC. POLEmuts are extremely rare, and the incidence of MSI-H and p53abn tumours is also quite low. Further subtyping of the NSMP subgroup is warranted.

Keywords: Microsatellite instability; Molecular subclassification; Next-generation sequencing; Ovarian clear cell carcinoma; Prognosis; TCGA subtypes.

MeSH terms

  • Adenocarcinoma, Clear Cell* / genetics
  • Adenocarcinoma, Clear Cell* / mortality
  • Adenocarcinoma, Clear Cell* / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Asian People / genetics
  • Biomarkers, Tumor / genetics
  • China / epidemiology
  • Class I Phosphatidylinositol 3-Kinases / genetics
  • DNA-Binding Proteins* / genetics
  • East Asian People
  • Endometrial Neoplasms* / classification
  • Endometrial Neoplasms* / genetics
  • Endometrial Neoplasms* / mortality
  • Endometrial Neoplasms* / pathology
  • Female
  • Humans
  • Microsatellite Instability
  • Middle Aged
  • Mutation*
  • Ovarian Neoplasms* / classification
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / mortality
  • Ovarian Neoplasms* / pathology
  • Prognosis
  • Transcription Factors* / genetics
  • Tumor Suppressor Protein p53 / genetics

Substances

  • ARID1A protein, human
  • Transcription Factors
  • DNA-Binding Proteins
  • PIK3CA protein, human
  • Tumor Suppressor Protein p53
  • Class I Phosphatidylinositol 3-Kinases
  • Biomarkers, Tumor
  • TP53 protein, human