A Study Of The Correlation Between TSH-Prx1-Trx-1-HIF-1 Signaling Pathway And Invasion And Metastasis Of Papillary Thyroid Carcinoma

Objective:By testing the expression level of 4 factors(TSHR,Prx1,Trx1,HIF-1α) in papillary thyroid carcinoma(PTC),we studied the correlation between the 4 factors and clinical features of PTC such as gender,age,histological type,invasion and T stage.The objective was to assess the significance of TSH-Prx1-Trx1-HIF-1 signaling pathway in invasion and metastasis of PTC.Method:We selected 34 resected Paraffin-embedded samples of classical PTC,39 of tall cell variant of PTC and normal thyroid tissues adjacent to cancer operated in tianjin cancer hospital from 2003 to 2007 randomly.The expression of TSHR,Prx1,Trx1,HIF-1αin samples were assayed by immunohistochemical staining.Result:1,The rate of immuno-positive staining Prx1 in PTC was higher than the normal thyroid tissues adjacent to cancer with significant difference(P＜0.05).In 73 cases of PTC,the positive expressin rate of Prx1 with local invasion was compared with that without local invasion,with lymph node metastasis with without metatasis,in tall cell variant of PTC with classical PTC,in stage T3 and T4 with stage T1 and T2,the former were all higher than the latter with significant difference between groups(P＜0.05).The expression of Prx1 in PTC was not related to the patients' gender,age,tumor size.2,The rate of immuno-positive staining Trx1 in PTC was higher than the normal thyroid tissues adjacent to cancer with significant difference(P＜0.05).In 73 cases of PTC,the positive expressin rate of Trx1 with local invasion was compared with that without local invasion,with lymph node metastasis with without metatasis,in tall cell variant of PTC with classical PTC,in stage T3 and T4 with stage T1 and T2,the former were all higher than the latter with significant difference between groups(P＜0.05).The expression of Trx1 in PTC was not related to the patients' gender,age,tumor size.3,The rate of immuno-positive staining HIF-1αin PTC was higher than the normal thyroid tissues adjacent to cancer with significant difference(P＜0.05).In 73 cases of PTC,when the positive expressin rate of HIF-1αwith local invasion was compared with that without local invasion,with lymph node metastasis with without metatasis,in tall cell variant of PTC with classical PTC,in stage T3 and T4 with stage T1 and T2,in group of tumor size≤2cm with between 2cm to 4cm with＞4cm,there were significant differences between groups respectively (P＜0.05).The expression of HIF-1αin PTC was not related to the patients' gender,age.4,The positive expressin rate of TSHR in PTC compared with the normal thyroid tissues adjacent to cancer,in tall cell variant of PTC with classical PTC,the former were all lower than the latter with significant difference between groups (P＜0.05).In conclusion,the reduced expression of TSHR was related to the dedifferentiation of the PTC.5,The rates of simultaneous immuno-positive staining of Prx1 and Trx1,Trx1 and HIF-1αin 73 PTC were 56.16%(41/73),54.79%(40/73)respectively.The positive relationship have been found between the expression status of Prx1 and Trx1,Trx1 and HIF-1α.Conclusions:1,The intensive expressions of Prx1,Trx1 and HIF-1αwere related to invasion and lymph node metastasis in PTC;2,The expression of Prx1 was correlated with the expression of Trx1 in PTC.So was Trx1 with HIF-1α.We concluded TSH could promote the development of thyroid carcinoma by TSH—Prx1—Trx1—HIF—1 signaling pathway;3,Though the rate of immuno-positive staining TSHR was lower than classical PTC, tall cell variant of PTC was more aggressive with higher positive expression rates of Prx1,Trx1 and HIF-1αthan classical PTC.We concluded that TSH conld promote the invasion and metastasis in thyroid carcinoma not only by TSHR but also by TSH—Prx1—Trx1—HIF—1 signaling pathway.Also we demonstrated the significance of thyroxine suppressive therapy,especially in poorly differentiated thyroid carcinoma with reduced expression of TSHR;4,In order to survive and proliferate,tumors could regulated the microenvironment to defend reactive oxygen species by TSH—Prx1—Trx1—HIF—1 signaling pathway.The signaling pathway will be a new target in PTC.