Abstract 19P
Background
Gynecological mesonephric-like adenocarcinoma (MLA) is a rare tumor type. Its morphology is similar to mesonephric adenocarcinoma but histological origin is unknown. The molecular pathological study of MLA is still in its preliminary stage. Poor prognosis and lack of diagnostic and therapeutic standards are the major challenges of this disease.
Methods
The medical records of patients admitted to West China Second University Hospital between January 1, 2010 and December 30, 2022 were retrospectively reviewed (Ethics number: 20220305). Total DNA and RNA were extracted from formalin-fixed paraffin-embedded (FFPE) tumor samples and peritumoral samples. Whole exon sequencing and mRNA sequencing were performed using AmoyDx® Tumor panoramic genetic testing kits (AmoyDx, Xiamen, China) and AmoyDx® Human transcription genetic testing kits (AmoyDx, Xiamen, China) respectively.
Results
A total of 17 cases of gynecological MLAs were identified, originating from three sites (cervix n=2, ovary n=5, uterus n=10). Median follow up time, progression free survival (PFS), and overall survival were 19 months, 14.5 months, and18.5 months respectively. High frequency of KRAS mutation was observed (82.4%). Enrichment of KRAS signaling was observed simultaneously at the RNA level. Mutations in PIK3CA and SPOP are also present at moderate frequencies (47.1% and 23.5%) and mutually exclusive. Signature 15 and NNAT CNV gain were associated with poor prognosis. Upregulating of G2M checkpoint, E2F targets, and epithelial-mesenchymal transition (EMT) were main tumor-associated features of MLA. 16 kidney development related genes were identified upregulate in MLA, which was also significantly highly expressed when compared to TCGA UCEC/CESC/OV datasets. MLA exhibited a lower immune response potential, including lower lymphocyte infiltration and IFN scores when compared with peritumoral samples and UCEC/CESC/OV.
Conclusions
KRAS mutation is a key driver event in MLA. Kidney development related genes are important transcriptomic differences between MLA and other gynecologic tumors. Low immune response may limit the efficacy of PD-1/L1 therapy in MLA.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
C. Peng, J. Wang, C. Zhu: Financial Interests, Institutional, Full or part-time Employment: Amoy Diagnostics Co., Ltd.. All other authors have declared no conflicts of interest.