The Expression And Significance Of Tumor Necrosis Factor Receptors And Signal Transduction Protein TRAF2 In Thyroid Carcinoma

Objective: To investigate the expression of TNF receptors and signal transduction protein TRAF2 and their relationship with clininopathological factors and apoptosis in thyroid carcinoma, so as to study the role of TNF receptors and TRAF2 in thyroid carcinoma. Methods and results: 41 thyroid carcinomas, 9 thyroid adenomas and 7 normal thyroid tissues adjacent to adenomas were investigated quantitatively for the expression of TNFR1, TNFR2 and TRAF2, using immunohistochemical staining SP method. Simultaneously, terminal deoxynucleotidy1 transferase (TdT)-mediated dUTP-digoxigenin nick end labelling method (TUNEL) was performed to detect semiquantitatively the presence of apoptosis. TNFR1 and TNFR2 were found to be expressed highly in only thyroid carcinoma specimens; their positive rate (gray value) of TNFR1 and TNFR2 were 60.98% (123.84±13.05), 65.85%(116.72±16.12), respectively. However, TNFR1 and TNFR2 were very low in thyroid adenoma and negative in normal thyroid tissues. TRAF2 was found in most thyroid tissue specimens, its positive rate(gray data) in carcinoma, adenoma and normal tissues was, respectively, 80.49%(105.11±10.97), 66.67(116.11±12.67) and 47.15%(125.03±14.91). Statistic analysis showed that TNFR1, TNFR2 and TRAF2 in carcinomas were higher than those in adenomas and normal tissues, but there was no significant difference in adenoma and normal tissue. Interestingly, we found TNFR1, TNFR2 and TRAF2 in papillary thyroid carcinoma were higher than those in follicular thyroid carcinomas(TNFR1,P<0.05;TNFR2,P<0.001;TRAF2,P<0.01). But they were not related to other clinicopathologic factors. TNFR1 is positively related to TNFR2(r=0.77). TRAF2 had a positive relationship with TNFR1 or TNFR2(r=0.43 or r=0.46). No apoptosis was detected in normal thyroid tissues and thyroid adenomas. Apoptosis was seen in thyroid carcinomas, but its rate was very low. No apoptosis was detected in 54.55% of papillary carcinomas and 75% of follicular carcinomas. Low apoptosis rate was demonstrated in 39.39% papillary carcinomas and 25% follicular carcinomas. 6.06% of papillary carcinomas showed a high apoptosis rate, with TRAF2 negativity. In 6 of 8 carcinomas with TRAF2 negativity, apoptosis was detected. Correlation analysis demonstrated a significant relationship between apoptosis and TRAF2 expression in thyroid carcinomas(r=-0.49), whereas no relationship was seen with TNFR1 or TNFR2. Conclusions: The data suggest the abnormal expression of TNFR1, TNFR2 and TRAF2 may play an important role in the carcinogenesis of thyroid carcinoma. Apoptosis occurs infrequently in thyroid carcinoma and it is not related to chinicopathological factors. TNFR1 or TNFR2 is not related to thyroid carcinoma cell susceptibility to apoptosis. Moreover, TRAF2 can inhibit apoptosis in thyroid carcinoma. TNFR1 and TNFR2 are two pathological indexes for diagnosis and differential diagnosis of thyroid carcinoma, but they are not used to assess the biological behaviors and prognoses of thyroid carcinoma. Perhaps TNF-induced apoptosis may be increased by inhibiting TRAF2, so that TRAF2 may be a biomarker of genictherapy or immunotherapy for thyroid carcinoma. Certainly, further confirmatory studies with larger sample size are warranted and preformed.