Assosiation Of Expression Of Sodium Iodide Symporter And Aggressive Variants Of Papillary Thyroid Carcinomas

ObjectiveThis study explored the distinctions of clinical feature of different variants of papillary thyroid carcinoma (PTC).We detected sodium iodide symporter (NIS) protein and mRNA in different variants of PTC and normal thyroid tissue. Meanwhile assosiation of expression of NIS and aggressive variants of PTC was analyzed.Methods135cases of PTC were collected in Tianjin cancer hospital from February2011to February2012, including45cases of tall cell variant,45cases of diffuse sclerosing variant,45cases of classic variant. And normal thyroid tissue of the above cases,45cases of nudolar goiters were collected as the control group. All these cases were cinfirmed by Pathology Department. This study explored the distinctions of clinical feature of different variants of PTC. NIS protein was evaluated by immunohistochemi stry, while NIS mRNA was quantified by RT-PCR. Clinical data was evaluated using SPSS17.0statistical software package. NIS expression was analyzed with x2tests and non-parametric tests. P<0.05was considered statistically significant.Results1、 Statistical results for clinical feature of of different variantsIn extra thyroidal invasion, there was significant difference between tall cell variant and classic variant,(P=0.035). No relationship was found in age, gender, tumor size, lymph node metastasis, TNM stage, multifocality between the two groups. No relationship was also found in age, gender, tumor size, extra thyroidal invasion, lymp-h node metastasis, TNM stage, multifocality between diffuse sclerosing variant and classic variant.2、 Results of immunohistochemistry2.1The expression and cellular localization of NIS proteinThe positive expression rate of NIS protein in tall cell variant (35.5%), diffuse sclerosing variant(44.4%), classic variant (62.2%) was higher than that in normal thyroid tissue(22.2%、20.0%、26.7%), and nodular goiter(20.0%).NIS protein levels tended to be significantly lower in tall cell variant than that in classic variant (35.5%VS62.2%),(P=0.034). NIS protein levels tended to be significantly lower in diffuse sclerosing variant than that in classic variant (44.4%VS62.2%),(P=0.041).The immunohistochemistry result showed that NIS expressed in cytoplasm in97cases (71.8%), in nucleus in26cases (19.2%), in cytoplasm and nucleus in10cases (7.4%), in cell membrane in2cases (1.5%).2.2The correlation between the expression of NIS protein and clinicopathological pa rameters of PTCThe positive expression rate of NIS protein in tumors with extra thyroidal invasion was significantly lower than that in tumors without extra thyroidal invasion,(P=0.029). No relationship was found between expression of NIS protein and gender, age, tumor size, lymph node metastasis, TNM stage, multifocality.3、Results of RT-PCR3.1The expression of NIS mRNA for paired thyroid tissues.The number of patients whose NIS mRNA△CT of cancer tissue was higher than that of normal thyroid tissue was81, with mean rank14.64, while the number of patients whose NIS mRNA△CT of normal thyroid tissue was higher than that of cancer tissue was41,with mean rank6.00,(P=0.00). NIS mRNA levels tended to be significantly lower in PTC than that in paired normal thyroid tissue.3.2The expression of NIS mRNA for variants of PTCThe positive expression rate between tall variant and classic variant existed no significant differences,(P>0.05).There was also no significant differences between diffuse scleosing variant and classic variant,(P>0.05).3.3The correlation between the expression of NIS mRNA and clinicopathologic para meters of PTCNIS mRNA△CT in tumors whose diameter were larger than2centimetre (23.10) was higher than in tumors whose diameter were smaller than2centimetre (14.35).It suggested that NIS mRNA of the former group was lower than in the latter group. No relationship was found between expression of NIS mRNA and gender, age, extra thyroidal extension, lymph node metastasis, TNM stage, multifocality.Conelusion1、 NIS protein levels in tall cell variant and diffuse sclerosing variant was lower than that in classic variant relatively.The low expression of NIS may be related to invasive nature of tall cell variant, diffuse sclerosing variant.2、 NIS protein levels in cancerous tissue was higher than in normal thyroid tissue while NIS mRNA levels in cancerous tissue was lower than in normal thyroid tissue. This suggested that anomalous expression of NIS at translational level is the main reason for its high expression in tumor cells.3、 Correlation was found between expression of NIS and extra thyroidal invasion, tumor size. NIS protein in tumors with extra thyroidal invasion is lower than that in tumors without extra thyroidal invasion. NIS mRNA in tumors whose diameter were lager than2centimetre is lower than that in tumors whose diameter were smaller than2centimetre.4、 Overexpression of NIS for PTC is mainly targeted in intracellular cytoplasm not the functional plasma membrane. These carcinnomas are insensitive for radioactiv e iodine therapy, for they lack the ability of iodide-concentrating.