Objective To investigate the mRNA,protein expression and tyrosine phosphorylation of insulin receptor substrate.1(IRS-1)in endometrial carcinoma.Methods Sixty-three endometrial carcinoma(EC)patients,21 endometrial atypical hyperplasia(AHE)patients and 22 normal control(NE) entered this smdy.Their clinical information were colleeted Fasting serum C-peptide concentration was measured.Expression of IRS-1 in endometrium was examined by RT-PCR and western blol Immunoprecipitation was used to measure the tyrosine phosphorylation of IRS-1.Results C-peptide 0.007].There were no significant differences in IRS-l mRNA and protein expression among the three grouDs.Tyrosine phosphorylation of IRS-1 in EC group[(62±36)%]was higher than that in AHE and NE groups[(53 4-34)%and(35 4-33)%;P=0.048,0.002].IRS-1 activation in AHE group was also higher than nornlal control(P=0.045).IRs-1 activation in endometrioid carcinoma[(69 4-33)%]was higher than that in other histological types[(34±31)%;t=2.300,P=0.025].IRs-l tyrosine phosphorylation was significantly higher in patients with advanced stage,high grade,deep myometrial invasion and pelvic lymph node metastasis.IRS-l activation in endometrium was positively correlated with fasting sertlm C-peptide concentration(r=0.491,P=0.001).Conclusions There is excessive activation of IRS-1 in endometrial carcinoma and atypical hyperplasia.Activation of IRS-I in endometrial carcinoma is related with poor clinical-pathologic fleatures and may be a prognostic predictor for this tumor.Over-activationof IRS-1 may be an intermediate event linking the hyperinsulinemia and endometrial carcinoma.