| ObjectivesThyroid cancer is one of the most common cancers,although most of Differentiated Thyroid Carcinoma(DTC)has a nice prognosis,there is about 5%of the patients who suffer distant metastases.About 2/3 of these distant metastases patients are similar to undifferentiated carcinoma and lose the ability to uptake radioiodine.These patients together with patients who have undifferentiated carcinoma are referred to as Refractory Radioiodine Thyroid Cancer.The prognosis of RAI-R DTC is relatively poor.The difference of prognosis between RAI-R DTC and common DTC is significantly big.This research aims to explore and demonstrate the possible reason responsible for the phenomenon by doing IHC of specimen from RAI-R DTC collected in Qilu hospital during the time from 2002 to 2015 from the patients who received 131I treatment.Using IHC to test the expression levels of NIS,OCT4 and CD133.This research also aims to explore the molecular mechanism of RAI-R DTC and provide new treatment strategy for clinical patients.MethodsCollect clinical data of patients who have received 131I treatment between 2002 to 2015,choose the patients who aapply to?2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer?and collect the specimens with the permission of the patients to conduct IHC research to explore and test the certain proteins CD 133,OCT4 and NIS expression.It was demonstrated that protein NIS may be responsible for the insensitive to 131I treatment,therefore,we choose NIS as one of the target proteins.OCT4 was reported to have relationship with the resistance of radiotherapy and relevant to the malignant characters of cancer cells,so OCT4 protein was selected to be one of our research proteins.As to CD 133,there are many papers said that CD 133 was thought to be biomarker of cancer stem cells and had relationship with resistance to traditional radiotherapy and chemotherapy.Above all,these proteins were supposed to have connections with resistance to chemotherapy and radiotherapy,or the ability in thyroid cancer of uptaking radioiodine.The negative control is the relatively healthy people who have thyroid nodules and the positive control is the patients who are sensitive to radioiodine and radioiodine therapy is effective to these patients.The experimental group is the RAI-R DTC.Results1.The NIS expression in RAI-R DTC and control group NIS expressed in cytoplasm in thyroid follicular cell and there was no expression in nucleus.(picture 1)The positive rate of NIS in RAI-R DTC group is 57.14%,while the NIS positive rate in RAI DTC group and control group reaches 100%.The Immunohistochemical score indicates:the score of RAI-R DTC group is 4.29± 1.77,RAI DTC group is 9.57± 1.57,control group is 10.14±0.94,the NIS positive in RAI-R DTC group is significantly lower than that in RAI DTC and control group.(Table 2)2.The OCT4 expression in RAI-R DTC and control groupThere is no OCT4 expression in control group,OCT4 expressed in nucleus in thyroid follicular cell and foci cells in RAI-R DTC and RAI DTC group,there is no OCT4 expression in cytoplasm(picture 1)?In RAI-R DTC and RAI DTC group,the OCT4 expression positive rates are 100%,besides,there is no statistical difference in immunohistochemical score in the two groups.3,The CD133 expression in RAI-R DTC and control groupThere is CD 133 expression in cytoplasm and membrane in thyroid follicular cell and foci cells in RAI-R DTC group.The CD 133 expression positive rate is 71.43%in RAI-R DTC group,the CD133 positive rate in RAI DTC group is 42.85%,there is no CD133 expression in control group.The final immunohistochemical score indicates:RAI-R DTC group is 6.86±2.14,RAI DTC group is 1.71 ±0.92(Table 1),the CD 133 expression positive rate and immunohistochemical score in RAI-R DTC group is significantly higher than RAI DTC and control group.(picture 1.P<0.05)?Conclusion1.The possible reason for radioiodine refractory thyroid cancer is low expression of NIS,leading to reduce of iodine transduction from extracellular to intracellular and the reduce in iodine intaking and accumulation.2.Although,there is no OCT4 expression in control group,there is high OCT4 expression in both RAI-R DTC and RAI DTC groups,indicating that OCT4 is not the possible reason for the resistance of radiotherapy.However,OCT4 protein has important meaning to thyroid cancer development.3.CD133 expression is significantly higher in RAI-R DTC group than RAI DTC and control group. |
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