Abstract 768P
Background
High grade serous ovarian cancers (HGSC) without pathogenic variants in the BRCA1/2 genes have worst clinical outcomes and less therapeutic options. P-cadherin (P-cad) is a transmembrane glycoprotein involved in cell-cell adhesion that has been reported to be overexpressed in epithelial ovarian cancer (EOC). Nevertheless, its impact in patients without BRCA1/2 mutations remains unknown. The aim of this work was to characterize the expression of P-cad in HGSC and its association with overall survival, according to BRCA1/2 mutational status.
Methods
Chemo-naïf HGSC were selected from a consecutive case series of non-mucinous EOC cases treated in a single cancer centre and tested for BRCA1/2 deleterious variants by next generation sequencing (1/2016 - 6/2020). P-cad expression was evaluated using immunohistochemistry and quantified with H-scoring system (QuPath® software). Group comparisons were made using T-test and X2, where appropriate. Survival analyses were computed with Kaplan-Meier estimator and log-rank test.
Results
A total of 116 samples from 78 patients were analysed (63 primary tumours / 53 metastasis; 38 matched pairs). Deleterious variants in BRCA1/2 were present in 21.8% of patients (BRCA-mt). Median age 59 years-old; 67.9% FIGO stage III. BRCA-mt and BRCA wildtype (BRCA-wt) patients were balanced regarding these baseline features. Primary tumours expressed variable levels of P-cad (mean H-score 131.3, sd 86.3), displaying intra and inter-tumoral heterogeneity. Expression levels were concordant between primary tumours and matched metastasis; mean H-scores did not differ between BRCA-mt and BRCA-wt. Tumours with high P-cad expression (H-scores >=130) were significantly associated with worst overall survival only in the BRCA-wt subgroup (p<0.05).
Conclusions
Our results suggest that overexpression of P-cad may be a prognostic biomarker in BRCA-wt patients. Further studies are needed to validate these data in a larger and prospective cohort.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Porto.Compreensive Cancer Center (P.CCC).
Funding
Fundação para a Ciência e Tecnologia (FCT).
Disclosure
All authors have declared no conflicts of interest.