Study Of EGFR, NF-kB Expression And EGFR Mutation In Endometrial Cancer

Background and Objective:Endometrial carcinoma(EC)is one of the most common malignant tumors of thefemale reproductive system, although the treatment technology for endometrialcancer was developing currently, it's still difficult to treat the advanced and recurrentendometrial carcinoma. Epidermal growth factor receptor (EGFR) is a across filmreceptor type tyrosine kinase, its regulate the development of tumor through signalpathway. Studies have shown that there was the expression of EGFR in endometrialcarcinoma, is related with the targeted therapy, occurrence, development ofendometrial cancer. Also, the EGFR tyrosine kinase inhibitor can raise the effect ofradiation treatment to the tumor cells which show highly expression of EGFR. Therewas a high mutation rate of EGFR to the persons who displayed a sensitive treatmentto the EGFR tyrosine kinase inhibitor in NSCLC. The EGFR mutation has a closelyrelated with the effect of EGFR tyrosine kinase inhibitor treatment. Whether theEGFR mutation exist in the EC and the relationship of the EC treatment are theimportant point which we were working for, it's very important for the treat to theEC.NF-kB is one of the most important nuclear transcription factor, it's participatein the process of multiple signal transduction about gene regulation, immune responseand apoptosis,P50or p65is one of the most widely distributed heterogeneous dimmer.Research displayed that NF-kB and EGFR were expressed in nasopharyngealcarcinoma, esophageal cancer and other tumors, and their relationship was positivecorrelation. Both of them plays an important role in the occurs, development andinvasion of tumor. However,there were no research report about the relationship ofNF-kB and EGFR in endometrial carcinoma. Whether EGFR and NF-kB play acollaborative role in endometrial carcinoma is still unknown, it's of great significanceto detect the relationship of EGFR and NF-kB protein expression.Methods:1. Paraffin-embedded tissues of endometrial were obtained from104patients `who underwent in the Second Affiliated Hospital of Nanchang University and TumorHospital of Jiangxi Province. There were30cases of normal proliferative endometrial,18cases of endometrial atypical hyperplasia and56cases of endometrial carcinoma.Immunohistochemistry were used to detect the expression of EGFR and NF-kB in thedifference endometrial. Some statistical methods such as X2test and Fisher exactprobability combined with analysis of clinical data were used to statistics.2. Take the above-mentioned56cases of tumor Paraffin-embedded tissues,fresh surgical specimens of19cases of endometrial cancer as the experimental groupand30cases abnormal endometrial tissues due to vaginal bleeding to Curettage forthe control group. Genomic DNA was extracted from specimen The genes fragmentsin coding regions and regulatory regions of EGFR tyrosine kinase domain wereamplified specifically by polymerase chain reaction (PCR). Then gene sequencingwas conducted, the results were compared with the standard sequence.Results:1. The positive expression rate of EGFR protein in the normal proliferativeendometrial, endometrial atypical hyperplasia and endometrial carcinoma werereduced gradually (30.0%,44.4%,73.2%; p＜0.05). The positive expression rateof EGFR protein in endometrial carcinoma of histological differentiation were G166.7%, G274.1%, G381.8%;(p＜0.05),respectively. The positive expression rate ofEGFR protein were correlated to histological differentiation and myometrialinvasion (p＜0.05), but not to pathologic stage and lymph node metastasis(p＞0.05).2. The positive expression rate of NF-kB protein in the normal proliferativeendometrial, endometrial atypical hyperplasia and endometrial carcinoma werereduced gradually (13.3%,38.9%,64.2%; p＜0.05). The positive expression rateof NF-kB protein in endometrial carcinoma of histological differentiation were G155.6%, G263.0%, G381.8%;(p＜0.05),respectively. The positive expression rate ofEGFR protein were correlated to histological differentiation and myometrialinvasion (p＜0.05), but not to pathologic stage and lymph node metastasis(p＞0.05).3. There was1case mutation was found in coding region of EGFR tyrosine kinase domain in the exon19(G2281A), no mutation was found in coding region ofEGFR tyrosine kinase domain in the exon21. No mutation was found in otherexperimental specimens.Conclusions:1. The expression rate and intensity of EGFR and NF-kB protein was correlatedwith histological grade and the depth of muscular layer infiltration, the worse tumordifferentiation, the higher rate of positive expression, the higher depth of muscularlayer infiltration, the higher rate of positive expression；2. EGFR expression was significantly correlated with NF-kB;3. There was a gene mutation in the exon19in one case of endometrialcarcinoma.