Uterine Clear Cell Carcinoma (UCCC)

Overview

UCCC (Uterine Clear Cell Carcinoma) is a rare, high-grade endometrial carcinoma subtype with clear-cell histology, classified as a child of UCEC in OncoTree. It is histologically distinct from endometrioid (UEC) and serous (USC) endometrial carcinomas but overlaps with both molecularly; approximately one-third of CCECs show serous-like profiles (TP53/PPP2R1A co-mutation) and one-fifth show endometrioid-like profiles (PTEN/KRAS/ARID1A mutations). MSI is present in ~11% of cases. The largest exome-scale characterization was the NIH study (uccc_nih_2017, n=63) that nominated TAF1 and KMT2C as novel candidate drivers.

Cohorts in the corpus

  • uccc_nih_2017 — 63 clinically diagnosed CCEC cases (16 paired exomes, 47 Sanger-validated); NIH, Le Gallo et al. 2017.

Recurrent alterations

Subtypes

  • Serous-like (group 1): TP53 + PPP2R1A co-mutation; 27.0% of CCECs; resembles USC.
  • Mixed (group 2): 19.1%; intermediate molecular features.
  • Endometrioid-like (group 3): PTEN/KRAS/ARID1A enrichment; 20.6%; resembles UEC.
  • No detectable alteration across the 7-gene + MSI panel: 33.3% — likely harbor drivers outside the surveyed loci.

Therapeutic landscape

  • 11.3% MSI rate supports consideration of anti-PD-1 therapy (pembrolizumab); two MSI endometrial cancer patients responded to pembrolizumab in a phase 2 trial (Le Gallo et al.). PMID:28485815
  • 34.9% PI3K-axis mutation rate (PIK3CA/PIK3R1/PTEN) implies potential vulnerability to PI3K/AKT/mTOR-axis inhibitors. PMID:28485815

Sources

  • PMID:28485815 — Le Gallo et al., whole-exome sequencing of 63 uterine clear cell carcinomas (uccc_nih_2017).

This page was processed by crosslinker on 2026-05-15.