Expression And Clinical Significance Of TFF3and SDF-1/CXCR4in Patiens With Papillary Thyroid Carcinoma

Thyroid carcinoma,which is a multiple-gene and multiple-factor regulated cancer with a2.59%incidence is one of the most common endocrine malignancies.On Clinical fingings show that,5%～15%of thyroid Nodes are thyroid carcinoma,80%are PTC diagnosed by palpation, colour doppler ultrasound, radionuclide imaging and fine needle aspiration cytology(FNBC) and so on.However, these methods cannot distinguish begin from malignant thyroid Node well.Tumor markers that are highly sensitive and strongly specific play an important role in the diagnosis and therapy of thyroid carcinoma.Hence,exploring new diagnosis methods to increase the diagnostic rate of thyroid carcinoma is a hot research area. This experiment aims to detect the expression of TFF3, SDF-1/CXCR4protein and mRNA in surgical specimens by immunohistochemistry(IHC) SP, in situ hibridazation(ISH) and RT-PCR methods.In additions, ELISA method is used to determine the serum TFF3level in different kinds of tyroid tumors.In order to provide experimental basis for the diagnose and targeted therapy of papillary thyroid carcinoma, the role of TFF3, SDF-1/CXCR4on the occurrence,development and preoperative diagnosis of papillary thyroid carcinoma are disscussed.The Pathological tissue with tyroid tumor of patients who have operative treatment in Department of Otorhinolaryngology Head and Neck Surgery of the First Affiliated Hospital of Hebei North University is collected. According to2004WHO Pathological Histology classificatory criteria:92cases of thyroid papillary carcinoma,male30,female62.The average age is23～75.Among92cases, those43cases under the age of45, the others are over the age of45. There are74cases of tumours diameter over1.0cm. Patients are staged according to TNM (UICC) staging system and distributed as follows:33of stage1-11,59of stage III-IV. Imunohistochemistry(IHC) SP is used to detecet the TFF3, SDF-1and CXCR4protein; in situ hibridazation(ISH) and RT-PCR are used to detect TFF3,SDF-1and CXCR4mRNA.At the same time,papillary thyroid carcinoma tissue chip is purchased to verificate expression of TFF3,SDF-1,CXCR4of different sources of specimens,so as to acquire the exact data.HE staining shows the characteristic feature of being the irregular in shape and glass nuclei of the PTC.And IHC,ISH staining shows the positive matters of TFF3protein and mRNA are brown granules in cytoplasm of pillar cells with different thickness, which distribute closely and are expressed highly.While in folicular cells of paracarcinomatous are in the shape of cube and TFF3is negtive. The positive rate and AOD value of TFF3is significantly higher in tissues with lymph node metastasis than in those without metastasis (100%vs86.27%, P=0.012),however,it has nothing to do with gender and age. There is high expression of SDF-1in the cytoplasm of malignant tissues, weakly positive or negative in peri-cancerous tissue and weakly positive in metastatic lymph nodes. CXCR4mainly expressed in cytoplasm and minority in nuclei, while negative in peri-cancerous tissue. The positive rate and AOD values of SDF-1protein are similar to that of CXCR4in PTC,that is to say positive rate and AOD values in stage Ⅲ～Ⅳ are higher than that in Ⅰ～Ⅱ,higher in cases of lymph node metastasis than in those without lymph node metastasis, higher in patients over45than that in patients under45.In situ hibridazation shows that the high expression rates of TFF3mRNA and SDF-1/CXCR4mRNA are correlated with the TNM stage and lymph node metastasis(P<0.01). RT-PCR shows that the expressions of TFF3, SDF-1/CXCR4mRNA in patients with papillary thyroid carcinoma are significantly higher than those in normal group, adenoma and papillary hyperplasia group (P<0.01or P<0.05). There is a positive correlation between TFF3with SDF-1and SDF-1with CXCR4(r=0.971, P=0.001).The concentration of TFF3in serum with PTC is the highest among the four groups (P<0.001).Serum concentrations of TFF3in surgical specimens with TFF3positive group are obviously higher than that in the negative group (P<0.05).Therefore, the following conclusions can be reached:1. The high expressions of TFF3protein and mRNA in PTC have significanct reference value in judging the ccurrence,development and preoperative diagnosis.2. The positive expression of SDF-1/CXCR4is important to lymphatic metastasis, and promises to provid directions for targeted therapy of papillary thyroid carcinoma.3. There is a close correlation between TFF3and SDF-1/CXCR4in the development and turnover of PTC.