Frizzled-9 Expression Is Associated With Aggressive Clinicopathological Features and Reduced Overall Survival in Invasive Breast Carcinoma.

The Wnt/Frizzled signaling pathway is implicated in tumor progression, yet the expression patterns and regulatory dynamics of Frizzled class receptor 9 (FZD9) in breast cancer remain poorly defined. This study evaluated FZD9 protein expression in breast tumors and explored its transcriptional modulation in breast cancer cell lines exposed to cytotoxic and epigenetic agents. Immunohistochemical analysis was performed in 81 breast cancer cases representing major molecular subtypes. In parallel, breast cancer cell lines were treated with trichostatin A, 5-aza-2'-deoxycytidine, cisplatin, doxorubicin, paclitaxel, and ionizing radiation, followed by quantification of FZD9 mRNA levels by RT-qPCR. FZD9 protein expression was more frequent in HER2-enriched tumors, cases with high Ki-67 index, and advanced T-stage. FZD9-positive tumors were associated with reduced overall survival, whereas relapse-free survival showed no significant difference. Baseline FZD9 transcript levels varied substantially across cell lines, and transcriptional responses to chemotherapy, radiation, and epigenetic treatment were highly context-dependent, with divergent patterns observed according to molecular background. Collectively, these findings indicate that FZD9 expression in breast cancer is heterogeneous, associated with aggressive clinicopathological features, and dynamically modulated by therapeutic exposures, supporting its consideration as an exploratory marker of tumor aggressiveness and therapy-related biological responses.