Expression Of SLIT/Robo1 In Endometrial Cancer And Its Predictive Value Of Recurrence

Objective To investigate the potential predictive value of SLIT/Robol immunoreactivity in recurrent and non-recurrent endometrial cancers,and the relationship between SLIT/Robol immunoreactivity and microvascular density(MVD) in endometrial cancer.Methods From a total of 815 consecutive patients histologically diagnosed with endometrial cancer and 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 Robol.MVD counts were evaluated by CD34 immunohistochemistry.Univariate and multivariate analyses were performed to evaluate the effect of SLIT/Robol on recurrence risk with adjustment for other known risk factors.Results Immunoreactivity to pan-SLIT and Robol was higher in recurrent patients than that in non-recurrent patients.Both SLIT and Robol immunoreactivities were positively correlated with MVD.Cox regression analysis identified SLIT,along with age and FIGO stage,as risk factors for recurrence.The resultant discrimination model yielded estimated and cross-validated sensitivity and specificity of 79%and 85%,respectively.Conclusions Increased immunoreactivity to SLIT is an important factor for recurrence of endometrial cancer,likely through attracting endothelial cells and promoting neovascularization.Thus,the SLIT immunoreactivity is likely a promising biomarker for recurrence and the SLIT/Robol system may be a potential target for reducing the recurrence risk in endometrial cancer. Objective Our study is to investigate effect of estrogen on SLIT2 expression in human endometrial cancer cells.Methods RT-PCR was performed to verify the expression of SLIT/Robo in endometrial cancer cells.RT-qPCR(real-time PCR) was utilized to detect the change of SLIT2 mRNA expression at different time point treated with different dose of estradiol with/without progestogen in human endometrial cancer cells.Results Expression of SLIT/Robo in endometrial cancer cells was mainly SLIT2 and Robol.SLIT2 mRNA was up-regulated with estradiol treatment compared with control.Further study revealed that the most impact of estradiol on SLIT2 expression was observed when cells was treated with 10-8mmol/L estradiol,these impacts appeared from 12 hour and lasted to 72 hours after estradiol treatment.Conclusions Estradiol could up-regulate SLIT2 mRNA expression with dose and time dependence,and reversed by progestogen.