Increased SLIT Immunoreactivity As a Biomarker for Recurrence in Endometrial Carcinoma

Objective: We sought to investigate the potential predictive value of SLIT/ROBO1 immunoreactivity in recurrent and nonrecurrent endometrial cancer (EC), and the relationship between SLIT/Roundabout (ROBO1) immunoreactivity and microvessel density (MVD) in EC.

Study Design: From a total of 815 consecutive patients histologically diagnosed with EC who had undergone surgery we retrieved 45 patients who had confirmed recurrence and randomly selected 110 patients without recurrence. Their paraffin-embedded tissue blocks were also retrieved and subjected to immunohistochemistry for pan-SLIT and ROBO1. MVD counts were evaluated by CD34 immunohistochemistry. Univariate and multivariate analyses were performed to evaluate the effect of SLIT/ROBO1 on recurrence risk with adjustment for other known risk factors.

Results: Immunoreactivity to pan-SLIT and ROBO1 was higher in recurrence patients than that in nonrecurrence patients. Both SLIT and ROBO1 immunoreactivities were positively correlated with MVD. Cox regression analysis identified SLIT, along with age and International Federation of Gynecology and Obstetrics stage, as risk factors for recurrence. The resultant discrimination model yielded estimated and cross-validated sensitivity and specificity of 79% and 85%, respectively.

Conclusion: Increased immunoreactivity to SLIT is an important factor for recurrence of EC, likely through attracting endothelial cells and promoting neovascularization. Thus, the SLIT immunoreactivity is likely a promising biomarker for recurrence and the SLIT/ROBO1 system may be a potential target for reducing the recurrence risk in EC.