Molecular characterization and comparison of epithelial ovarian carcinoma (EOC) and primary peritoneal carcinoma (PCC)

Background

EOC and PPC are two cancers currently treated in a similar manner. Molecular tumor profiling, with its emphasis on individualized therapy, is altering prior treatment paradigms by focusing on molecular aberrations rather than organ primary to guide therapy. Studies at our institution on EOC and PPC suggest these are two distinct cancer types, with PPC being more aggressive. The aim of this study is to identify further differences in the molecular profiles of EOC and primary peritoneal carcinoma in order to identify treatment/resistant mechanisms and clinical trial opportunities.

Methods

In total, 5,685 EOC and 521 primary peritoneal carcinoma specimens were evaluated (Caris Life Sciences) by immunohistochemistry (IHC), in situ hybridization (ISH), fusion gene analysis, and next-generation sequencing (NGS). Initial diagnosis was made by the submitting institution and confirmation of diagnosis was made by a pathologist at the centralized laboratory.

Results

Significant differences were found between IHC and NGS. Protein expression in androgen receptor (28.8% v. 36.5%, p = 0.0011), EGFR (48.9% v. 59.0%, p = 0.0081), ER (46.0% v. 55.6%, p = 0.0001), PD-L1 (9.5% v. 5.7%, p = p = 0.0300), PR (22.5% v. 14.6%, p = 0.0001), TLE3 (18.4% v. 13.2% p = 0.0120), TOP2A (75.9% v. 66.8%, p = 0.0001), and TS (54.3% v. 44.1%, p = 0.0001) varied significantly between EOC and PPC, respectively. Significant differences in mutation rates were found in CTNNB1 (3.3% v. 0.7%, p = 0.0033), KRAS (9.4% v. 3.7%, p = 0.0001), PIK3CA (9.3% v. 4.8%, p = 0.0027), PTEN (3.9% v. 1.6%, p = 0.0222), and TP53 (63.3% v. 74.5%, p = 0.0001). No significant differences were found in amplification rates, as measured by ISH and CNV by NGS.

Conclusions

Multiplatform profiling reveals various potential targets in ovarian and primary peritoneal carcinomas for investigational and drug therapy. Comparison of their genetic profiles reveals two distinct cancers. Dysregulation of the PIK3CA/AKT/mTOR pathway appears to be more common in EOC while loss of TP53 is a more common event in PPC based on this cohort. More studies are urgently needed to assess differences between EOC and PPC.

Clinical trial identification

Not applicable - no trial protocol number or release date.

Legal entity responsible for the study

N/A

Funding

Caris Life Sciences

Disclosure

D. Arguello, K. Russell, A. Voss: Employee (Caris Life Sciences) Stock (Caris Life Sciences) All other authors have declared no conflicts of interest.