Supplementary Material for: Grainyhead-like 2 expression is associated with disease progression, chemoresistance and poor survival in tubo-ovarian high-grade serous carcinoma

Introduction: Grainyhead-like 2 (GRHL2) regulates epithelial-to-mesenchymal transition (EMT) in cancer. This study analyzed the expression and prognostic role of GRHL2 in high-grade serous carcinoma (HGSC).
Methods: GRHL2 protein expression by immunohistochemistry was analyzed in 411 HGSC (198 effusions, 213 surgical specimens). Expression score was generated by combination of staining extent and intensity and was assessed for association with clinicopathologic parameters and survival.
Results: GRHL2 expression was significantly higher in effusions compared to surgical specimens in both analysis of all specimens (p<0.001) and patient-matched tumors (n=39 patients; p<0.001). Expression was additionally higher in post-chemotherapy compared to chemo-naive effusions (p<0.001). Higher GRHL2 score in effusions was associated with a trend for shorter overall survival (OS; p=0.088). Higher GRHL2 score in surgical specimens was significantly related to non-optimal (>0 cm) debulking (p=0.004), non-complete chemoresponse at diagnosis (p=0.003), primary chemoresistance (p=0.045), and shorter OS (p=0.038) and progression-free survival (PFS; p=0.024). Both OS and PFS findings remained significant in Cox multivariate analysis (OS: p=0.048; PFS: p=0.04).
Conclusion: GRHL2 is overexpressed in HGSC effusions compared to solid lesions, possibly reflecting altered EMT status. However, high expression in solid lesions is associated with chemoresistance and poor survival, possibly due to mediation of tumor cell migration and invasion.