Prognostic and Diagnostic Significance of Annexin A1 in ypT3 Locally Advanced Rectal Cancer Patients

The prediction of the therapeutic response and of the patient outcome following neoadjuvant chemoradiotherapy (nCRT) in rectal cancer (RC) is still a challenging issue. The role of Annexin 1 (ANXA1) in the modulation of the tumor cells' growth and metastasis has been recently demonstrated, being associated with aggressive pathological features and poor outcome in specific malignancies. The present study aimed to evaluate the association between ANXA1 expression, survival, and clinicopathological parameters of a group of patients diagnosed with ypT3 locally advanced rectal cancer (LARC) following nCRT. The study group consisted of 60 LARC patients with ypT3 tumor stage showing a tumor fragmentation pattern following nCRT. The clinicopathological characteristics and survival parameters in relation to ANXA1 immunohistochemistry characteristics and its scoring were evaluated. ANXA1 expression in tumor cells showed variable intense luminal membrane or combined luminal membrane and cytoplasmic location, excepting three negative cases. The statistical analysis demonstrated a significant association between high ANXA1 expression and ypN category (p < 0.001), perineural invasion (PnI) (p = 0.002), and lymphovascular invasion (LVI) (p = 0.021). Survival analysis showed that high ANXA1 expression is associated with a reduced overall survival (OS) (p = 0.001), while univariate Cox regression confirmed ANXA1 value as an independent predictor of prognosis (H = 5.922, p = 0.004). Our results support ANXA1 value as a potential biomarker of aggressive tumor behavior and poor prognosis in ypT3 LARC patients, with potential implications in diagnosis stratification, opening the prospective to apply precision oncology strategies. However, further studies are required to certify ANXA1 diagnostic and therapeutic relevance in RC patients.