Molecular portraits of clear cell ovarian and endometrial carcinoma with comparison to clear cell renal cell carcinoma

Authors:

Sarah A. Ackroyd, David Arguello, Haider Mahdi, Adam El Naggar, Ira Winer, Rob Holloway, Thomas Krivak, Nathaniel Jones, Valerie Galvan Turner, Thomas Herzog, Christina Chu, MD , Jubilee Brown, Gina Mantia-Smaldone

OBJECTIVE

To evaluate ovarian clear cell carcinoma (OCCC) and endometrial clear cell carcinoma (ECCC) using multiplatform profiling technology and compare their molecular profiles to clear cell renal cell carcinoma (ccRCC).

BACKGROUND

  • Ovarian clear cell carcinoma is rare, accounting for approximately 5-25% of epithelial ovarian cancers (EOC) with a higher prevalence in Asian women (1).
  • These tumors are high-grade, and women with advanced stage disease have a poorer prognosis than those with high grade serous EOC (2). Advanced clear cell gynecologic malignancies remain amongst the most challenging diseases to manage.
  • OCCCs have a high frequency of common genetic mutations including ARID1A and PIK3CA and higher expression of HNF1β compared to high grade serous EOC.
  • OCCCs have similar gene expression profiles compared to endometrial and renal CCCs (3).
  • Molecular profiling of clear cell ovarian cancer may help to identify new targeted therapy as well as predictive biomarkers.

METHODS

  • OCCC, ECCC, and ccRCC tumor samples were evaluated from 2015 to 2018 by Caris Life Science for multiplatform analysis (Caris Life Science, Phoenix, AZ).
  • Mutation analysis was performed using fragment analysis (FA), gene amplification with chromogenic in situ hybridization (CISH), and/or next-generation sequencing (NGS) with the NextSeq platform (Illumina, Inc., San Diego, CA).
  • Chi-square testes were used to determine molecular differences between subtypes.

CONCLUSIONS

  • OCCC and ECCC are similar diseases requiring novel approaches to treatment.
  • rcCCC, although pathologically similar, has differential mutation expression patterns than OCCC and ECCC.
  • rcCCC and OCCC/ECCC have common mutations in APC and PTEN.
  • Prospective clinical trials are needed to examine targeted therapies as well as checkpoint inhibition in these gynecologic disease subtypes.

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