Advanced mucinous ovarian cancer (mOC) is a chemo resistant disease with poor outcomes compared to serous ovarian cancer (sOC). It is often confused with mucinous colorectal carcinoma (mCRC) metastatic to the ovary. Studies have explored CRC chemo regimens for the treatment of mOCs due to their histologic similarities. Herein we use comprehensive technologies to further our understanding of mOC.
140 mOC specimens were evaluated by Caris Life Sciences from 2015 ‐2018 using next generation sequencing (NGS), fragment analysis (FA), in situ hybridization (ISH), and immunohistochemistry (IHC). 188 mCRC were used for comparison. Chi square analysis was conducted using SPSS.
The most frequent mutations in mOC were KRAS (64.7%), TP53 (56.0%), ARID1A (50.0%), CDKN2A(18.7%), PIK3CA (11.7%), and ATM (8.2%). ERBB2 (HER2) amplification was 12.2%. BRCA1 and BRCA2 mutation rates were 0.0 and 2.4%. Markers of immunogenicity were rare: MSI‐H in 4.2%, high tumor mutational burden (TMB) in 4.8%, and PD‐L1 expression in 5.3%.
Significant differences between mOC and CRC were found in the following pathways: Wnt (APC: 4.7 vs 61.7%), P13K/AKT/mTOR (ARID1A: 50.0 vs 0.0% and FBXW7: 3.7 vs 12.5%), MAPK (BRAF: 2.4 vs 11.9%), cell cycle control (CDKN2A: 18.7 vs 0.0%), as well as in ERBB2 (HER2) amplification (12.2 vs 0.0%), and hormone receptor expression (ER: 12.8 vs 0.0%, PR: 15.9 vs 0.0%). High rates of KRAS (64.7, 73.5%) and TP53 (56.0, 46.7%) mutations were common to both tumor types.
Compared to mOC, right‐sided CRC were more likely to have mutations in CDH1 (0.0 vs 6.7%) and PTCH1 (0.0 vs 6.7%), while left‐sided CRC were more likely to have mutations in FOXO3 (0.0 vs 5.9%) and IDH2 (0.0 vs 5.9%).Download Publication