High FOXA1 immunohistochemical expression is associated with adverse outcomes in HPV-positive cervical squamous cell
Milena Giulia Gonçalves1, Rossana Veronica Mendoza Lopez1, Rafaella Almeida Lima Nunes2
1Center for Translational Research in Oncology, Instituto do Cancer do Estado de Sao Paulo-ICESP, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo-FMUSP HC, Sao Paulo, Brazil; Comprehensive Center for Precision Oncology-C2PO, Universidade de Sao Paulo-FMUSP HC, Sao Paulo, Brazil.
Background:
Forkhead box protein A1 (FOXA1) is linked to cancer development in different anatomical sites. We previously demonstrated that FOXA1 markedly increases high-risk human papillomavirus (HPV) transcription by directly binding to the long control region (LCR). Herein, we aimed to assess FOXA1 expression and its prognostic significance in cervical cancer (CC).
Methods:
Patients with CC treated at the Instituto do Cancer do Estado de São Paulo (ICESP), Brazil, were included. FOXA1 levels were measured using immunohistochemistry (IHC).
Results:
Overall, FOXA1 staining was observed in 85% (208/245) of the samples, primarily localized in both the nucleus and cytoplasm (71%). High FOXA1 staining was more frequently detected in squamous cell carcinoma (SCC) compared to adenocarcinomas (ADC) (p = 0.003). High FOXA1 staining was significantly associated with HPV-positive CC (p = 0.005). It was also associated with worse overall survival (OS) and disease-free survival (DFS) when considering all CC samples, as well as when restricting the analysis to SCC cases. Among HPV-positive cases, high FOXA1 staining was also significantly associated with poorer OS and DFS in women with SCC. Finally, high FOXA1 staining was associated with poor OS (HR 1.79; 95% CI: 1.14-2.79; p = 0.011) and poor DFS (HR: 1.64; 95% CI: 0.98-2.74; p = 0.056) among SCC cases in comparison to cases with low/moderate staining. No association was found between FOXA1 levels and prognosis in ADC.
Conclusions:
Our data suggest that FOXA1 may be involved in HPV-induced carcinogenesis and could serve as a prognostic biomarker in patients with cervical SCC.