Прогностическое значение экспрессии натрий-йодного симпортера для высокодифференцированного рака щитовидной железы

The clue function of thyroid follicular cells is iodide (I) uptake and thyroid hormones production. NIS mediates the active transport of I into the thyroid follicular cells. It is impossible to perform effective ¹³¹I radioablation (¹³¹I RA) up to 10% of all differentiated thyroid cancer (DTC) owing to dedifferentiation and lost ability to cumulate I. To distinguish this group of patient preoperatively is difficult.

Aim.

To assess the utility of using membrane located NIS detection as marker of unfavorable prognosis for DTC after ¹³¹I RA.

Materials and methods.

We enrolled in our study retrospectively sixty patients with DTC operated from 2005 to 2008. Based on postop routine histology examination we performed TNM staging. Forty-five patients received ¹³¹I RA postoperatively. During 60 month of follow up recurrence were detected in 20 cases. In all 60 patients' level of membrane located NIS expression were detected immunohistochemicaly (IHC) in primary thyroid tumor. All statistical analysis performed using PC program Statistica 7.0.

Results.

We found that mean level of membrane located NIS expression in DTC is 4.5%, with maximum up to 10%, whereas mean level of NIS expression in normal tissue is 30—40%. Least mean level of NIS expression was in patients group with recurrence of DTC after ¹³¹I RA (p=0.00083). We proved that crutial for recurrence of DTC after ¹³¹I RA were decreased level of membrane located NIS expression less than 1%. As well as we found statistically significant correlation between Recurrence Free Survival (RFS) and level of NIS expression (p <0.005).

Conclusion.

Membrane location of NIS determines its functional activity, and membrane located NIS amount decreases in DTC. Detection of membrane located NIS in DTC has prognostic value.

1. Состояние онкологической помощи населению России в 2010 году / Под ред. Чиссова В.И., Старинского В.В., Петровой Г.В. — М.: ФГУ "МНИОИ им. П.А. Герцена" Минздрав-соцразвития России; 2011. [Chissov VI, Starinsky VV, Petrova GV, editors. Sostoyanie onkologicheskoi pomoshchi naseleniyu Rossii v 2010 godu. Moscow: FGU "MNIOI im. P.A. Gertsena"; 2011. (In Russ).]

2. Dohan O, De la Vieja A, Paroder V, et al. The Sodium/Iodide Symporter (NIS): characterization, regulation, and medical significance. Endocr Rev. 2003;24(1):48-77. doi: 10.1210/er.2001-0029.

3. Ryu K-Y, Senokozlieff ME, Smanik PA, et al. Development of reverse transcription-competitive polymerase chain reaction method to quantitate the expression levels of human sodium iodide symporter. Thyroid. 1999;9(4):405-409. doi: 10.1089/thy.1999.9.405.

4. Liang J. Differential expression of the Na+/I- symporter protein in thyroid cancer and adjacent normal and nodular goiter tissues. Oncol Lett. 2012. doi: 10.3892/ol.2012.947.

5. Mian C, Barollo S, Pennelli G, et al. Molecular characteristics in papillary thyroid cancers (PTCs) with no 131I uptake. Clin Endocrinol (Oxf). 2008;68(1):108-116. doi: 10.1111/j.1365-2265.2007.03008.x.

6. Riesco-Eizaguirre G. The oncogene BRAFV600E is associated with a high risk of recurrence and less differentiated papillary thyroid carcinoma due to the impairment of Na+/I- targeting to the membrane. Endocrine-Related Cancer. 2006;13(1):257-269. doi: 10.1677/erc.1.01119.

7. Castro MR, Bergert ER, Goellner JR, et al. Immunohistochemical analysis of sodium iodide symporter expression in metastatic differentiated thyroid cancer: correlation with radioiodine uptake. J Clin Endocrinol Metab. 2001;86(11):5627-5632. doi: 10.1210/jcem.86.11.8048.