Investigation of the expression of ZİP, ZO-1 and claudin-1 in thyroid tumors by immunohistochemistry and real-time PCR methods

The thyroid gland is one of the most important endocrine organs with vital functions for the human body. Microscopically, it consists of follicle epithelial cells and adjacent parafollicular C cells around a central colloid. These cells constitute the main sources from which thyroid neoplasms develop. Thyroid neoplasms are the most common endocrine malignancies. They are more common in women patients than men. Thyroid cancers are the second most common type of cancer in women after breast cancer in our country. It affects the quality of life and lifespan of the patients, mostly due to their metastasis potential to the neck region. ZIP4 is an intra-membranous zinc transmembrane protein. Zinc plays a central role in the activation of transcription factors, and zinc transporters such as ZIP4 regulate the activity of zinc-dependent transcription factors by changing the intracellular zinc level. It has been shown that this situation supports tumor migration, invasion, and EMT (epithelial-mesenchymal transition) processes. ZO-1 and Claudin-1 are important tight junction proteins that increase and decrease in amounts in various cancers. In normal cells, ZO-1 and Caudin-1 form special structures for epithelial cells to maintain tight junctions. In this study, we aimed to investigate the expression of ZIP4, ZO-1 and Claudin-1 in thyroid tumors and the relationship of this expression with tumor types and prognostic parameters. 66 cases selected among the thyroidectomy materials sent to Dicle University Medical Faculty Pathology Department between 2010-2019 were included in our study. Of these 66 cases; 20 of them are diagnosed with multi nodular goiter, 18 of them are papillary thyroid carcinoma, 11 of them are medullary thyroid carcinoma, 11 of them are follicular thyroid carcinoma, and 6 of them are anaplastic thyroid carcinoma. ZIP4, ZO-1 and Claudin-1 were studied in all cases by immunohistochemical and Real-Time PCR methods. Immunohistochemical and Real Time-PCR study results were compared with age, gender, histological subtype, surgical margin status and presence of metastasis. 8 Following the IHC and RT-PCR studies, significant differences were found between the IHC expression of ZIP4, Claudin-1 and ZO-1 and histological subtypes. ZIP4 and Claudin-1 tended to be expressed more in cases with tumors, while ZO-1 in cases with and without tumors. Different staining characteristics were observed according to histological subtypes with staining pattern with membranous and intracellular localization with Claudin-1, and intracellular staining was observed in all cases of medullary thyroid carcinoma. Expression of ZIP4 and Claudin-1 by RT- PCR showed a significant difference between histological subtypes, and this difference was not observed with ZO-1. It was observed that the presence of metastasis increased with the expression of ZIP4 and Claudin-1, and there was no significant change with ZO-1. Although the prognostic course of thyroid carcinomas is generally good, it can often cause severe surgical procedures such as neck dissection in cases with metastases. We think that Claudin-1 and ZIP4 expression can be used as an important marker in terms of showing poor prognosis and susceptibility to metastasis in thyroid tumors and developing targeted therapy. We think that the ZO-1 marker, which is highly expressed in non-tumor tissue, is not useful as a prognosis marker in thyroid tumors.