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Published on: August 19, 2021
Preoperative molecular classification of endometrial cancer: Validation through biopsy and matched hysterectomy
Takahiro Nozaki1, Ikuko Sakamoto1, Keiko Kagami1
1Department of Gynecology, Yamanashi Central Hospital, Yamanashi, Japan.
Objective:
To evaluate the concordance of molecular classification between preoperative endometrial biopsy and corresponding hysterectomy specimens in endometrial cancer, and to assess the feasibility of using biopsy specimens for genomic profiling and recurrence risk stratification.
Methods:
We retrospectively analyzed 116 patients with endometrial carcinoma or uterine carcinosarcoma treated between 2014 and 2024. Molecular classification was performed using the ProMisE algorithm based on immunohistochemistry (IHC) for mismatch repair (MMR) proteins and p53, along with POLE mutational analysis. In addition, targeted next-generation sequencing (NGS) with a custom 57-gene panel was performed on both biopsy and hysterectomy specimens to evaluate the concordance of gene mutations.
Results:
The concordance rates between biopsy and hysterectomy specimens were 97 % for MMR status, 96 % for p53 status, and 99 % for POLE mutations, with an overall molecular classification concordance of 91 %. NGS identified 1943 gene mutations, of which 714 (37 %) were classified as oncogenic. Among these, 64 % were shared between the two specimen types. Molecular classification using biopsy specimens effectively stratified recurrence risk (p < 0.001), with POLE-mutated tumors showing the most favorable outcomes and p53-abnormal tumors the poorest.
Conclusions:
Molecular subtyping and targeted panel sequencing using endometrial biopsy specimens are feasible and show high concordance with hysterectomy-based results. This approach allows for preoperative risk assessment and supports personalized treatment planning in endometrial cancer.
