High glypican-3 expression characterizes a distinct subset of ovarian clear cell carcinomas in Canadian patients: an opportunity for targeted therapy

The expression frequency and distribution of glypican-3 (GPC3) was retrospectively assessed by immunohistochemistry in 316 accurately phenotyped ovarian clear cell carcinoma (OCCC) specimens from Canadian patients. The study aimed to evaluate the prevalence of this biomarker in OCCC in a mixed-ethnicity Canadian population and to evaluate associations of GPC3 expression with clinicopathological parameters. Tissue microarrays with napsin A or HNF1β positive and WT1-negative OCCC specimens were evaluated using a GPC3 antibody clone 1G12. Membranous, cytoplasmic, and Golgi pattern GPC3 expression was noted in 184 of 316 (58.2%) cases; 63 of 316 (20%) cases showed high GPC3 expression (>50% of tumor cells were positive). GPC3 expression was not associated with age, stage, and residual disease after primary surgery. High GPC3 expression did not correlate with a specific morphological pattern or the presence of endometriosis. Furthermore, GPC3 expression was not significantly associated with survival in the entire cohort. Statistically significant association of high GPC3 expression was noted with higher body mass index, napsin A positivity, estrogen receptor (ER) negativity, and ARID1A retention. In a stratified analysis by ARID1A status, high GPC3 expression was significantly associated with unfavorable outcomes in cases with loss of ARID1A (n=10; log rank p=0.0048). Women diagnosed with OCCC and high GPC3 expression were also more likely to receive adjuvant chemotherapy. Considering the tumor-specific membranous expression of GPC3 in 58% of cases and high interobserver reproducibility, GPC3 immunohistochemistry is a robust predictive test for inclusion in clinical trials for GPC3-targeted therapies for OCCC.