HIF-1α falls short, ERCC-1 stands out: Predictive insights in locally advanced cervical cancer

This study aimed to evaluate the association between pretreatment immunohistochemical expression of hypoxia-inducible factor 1 alpha (HIF-1α) and excision repair cross-complementation group 1 (ERCC1) and clinical outcomes in patients with locally advanced cervical cancer (LACC) treated with definitive concurrent radiochemotherapy (cRCT).

Eighty-seven patients with histologically confirmed LACC who received definitive cRCT between 2005 and 2015 were retrospectively analyzed. Immunohistochemical staining for HIF-1α and ERCC1 was performed on pretreatment biopsy specimens, and H-scores were calculated semi-quantitatively. Receiver operating characteristic (ROC) curve analysis determined optimal cut-off values: ≤100 and >100 for HIF-1α, and ≤130 and >130 for ERCC1. Overall survival (OS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were estimated using the Kaplan-Meier method, and prognostic variables were analyzed with Cox regression models.

The median age was 57 years (range: 37-85). The five-year OS, LRFS, and DMFS rates were 57.8%, 69.7%, and 69.1%, respectively. In multivariate analysis, incomplete treatment response (p<0.001) and high neutrophil-to-lymphocyte ratio (p=0.042) were independent predictors of poor OS. For LRFS, tumor size >4 cm (p=0.048), incomplete response (p<0.001), and high ERCC1 expression (p=0.032) were identified as unfavorable prognostic factors. High ERCC1 expression also correlated with increased late toxicity (p=0.038). HIF-1α expression showed no significant association with any survival outcome.

High ERCC1 expression was an independent prognostic indicator for poor LRFS, suggesting its potential as a biomarker of radioresistance. In patients with elevated ERCC1, alternative non-platinum agents may be considered. HIF-1α had no predictive or prognostic value in this cohort.