Background:

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.

Methods:

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.

Results:

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%).