scholarly journals THE ROLE OF IMMUNOHISTOCHEMICAL MARKERS IN PREDICTING RECURRENCE OR DEATH IN PATIENTS WITH MEDULAR THYROID CANCER

Author(s):  
Oleh Duda ◽  
◽  
Nina Boyko ◽  
Roman Slipetsky ◽  
◽  
...  

Introduction. Medullary thyroid cancer (MTC) belongs to a class of rare neuroendocrine aggressive tumors and arises from parafollicular cells (C-cells). An important modern problem is the development of ways to predict the recurrence of this disease. The aim of the study is to determine the role of immunohistochemical tumor markers of medullary thyroid cancer in predicting recurrence or death. Materials and methods. The analysis of the prospective study included 22 patients with MTC, 5 of whom have developed a recurrence and 4 have died at the end of the 10-year (120 months) follow-up period. Immunohistochemical examinations were performed using monoclonal antibodies of tumor markers calcitonin, chromogranin A, vimentin and Ki-67. Results. The discrepancy between the data of histological and immunohistochemical examinations in MTC is 12.0%, which indicates the hyperdiagnosis of this nosology and argues the importance of performing immunohistochemical examinations to verify the diagnosis. Patients who had a recurrence of MTC had significantly (p <0.05) lower levels of calcitonin expression (5.00 [5.00; 5.00] points) compared with patients who did not relapse, where this figure was 6.00 [6.00; 7.00] points. In patients with MTC, an increase in calcitonin expression was significantly associated with an increase in chromogranin A expression (r = + 0.49, p = 0.02); a similar relationship was found for the proportions of immunopositive cells of these tumor markers: r = + 0.68, p = 0.001. At the same time, it was found that the increase in the level of calcitonin expression was apparently combined with the decrease in the level of Ki-67 expression (r = -0.52, p = 0.02). It was also found that the increase in the level of vimentin expression is combined with an increase in the expression (r = + 0.64, p = 0.001) and the proportion of immunopositive cells of chromogranin A (r = + 0.45, p = 0.038). Conclusions. Low levels of calcitonin expression are prognostically unfavorable markers for the recurrence of MTC. Specific tumor markers are important in the treatment process and for the dynamic monitoring of patients with MTC.

2020 ◽  
Vol 98 (3) ◽  
pp. 443-448
Author(s):  
Huan Wang ◽  
Jian Tang ◽  
Zhiwei Su

Medullary thyroid cancer (MTC) is the third most common thyroid cancer. RET (Rearranged in Transformation) gene mutations are considered as one of the major drivers of MTC. Vandetanib suppresses RET activity, and has shown promise in clinical trials. Unfortunately, acquired resistance to vandetanib has been observed in MTC, although the mechanism was largely unknown. We investigated the critical role of YAP (Yes-Associated Protein) on vandetanib resistance in MTC. For this, TT cells (medullary thyroid cancer cells) were treated with vandetanib for 3 months to generate a vandetanib-resistant cell line (TT-R). We investigated the role of YAP on vandetanib-resistance in TT-R cells by performing cell proliferation and colony formation assays, and examined the antitumor effects of YAP inhibitor and vandetanib in a mouse model of xenografted MTC. The TT-R cells displayed 6-fold higher IC50 to vandetanib than the TT cells. Overexpression of YAP resulted in resistance to vandetanib, whereas knockdown of YAP re-sensitized the TT-R cells to vandetanib. The YAP inhibitor synergized with vandetanib on tumor inhibition. Our results suggest that YAP plays an important role in acquired resistance to vandetanib in MTC, providing basis for combating MTC with YAP inhibitor and vandetanib.


Endocrinology ◽  
2016 ◽  
Vol 157 (3) ◽  
pp. 1289-1298 ◽  
Author(s):  
Jun Ishii ◽  
Takuya Yazawa ◽  
Tomohiro Chiba ◽  
Yukiko Shishido-Hara ◽  
Yuu Arimasu ◽  
...  

Abstract Mechanisms of endocrine secretory granule (SG) formation in thyroid C cells and medullary thyroid cancer (MTC) cells have not been fully elucidated. Here we directly demonstrated that PROX1, a developmental homeobox gene, is transcriptionally involved in SG formation in MTC, which is derived from C cells. Analyses using gene expression databases on web sites revealed that, among thyroid cancer cells, MTC cells specifically and highly express PROX1 as well as several SG-forming molecule genes. Immunohistochemical analyses showed that in vivo MTC and C cells expressed PROX1, although follicular thyroid cancer and papillary thyroid cancer cells, normal follicular cells did not. Knockdown of PROX1 in an MTC cells reduced SGs detected by electron microscopy, and decreased expression of SG-related genes (chromogranin A, chromogranin B, secretogranin II, secretogranin III, synaptophysin, and carboxypeptidase E). Conversely, the introduction of a PROX1 transgene into a papillary thyroid cancer and anaplastic thyroid cancer cells induced the expression of SG-related genes. Reporter assays using the promoter sequence of chromogranin A showed that PROX1 activates the chromogranin A gene in addition to the known regulatory mechanisms, which are mediated via the cAMP response element binding protein and the repressor element 1-silencing transcription factor. Furthermore, chromatin immunoprecipitation-PCR assays demonstrated that PROX1 binds to the transcriptional regulatory element of the chromogranin A gene. In conclusion, PROX1 is an important regulator of endocrine SG formation in MTC cells.


Surgery ◽  
2003 ◽  
Vol 134 (6) ◽  
pp. 866-871 ◽  
Author(s):  
Rebecca S Sippel ◽  
Jennifer E Carpenter ◽  
Muthusamy Kunnimalaiyaan ◽  
Herbert Chen

2021 ◽  
pp. 153694
Author(s):  
Maryam Zarkesh ◽  
Noman Arab ◽  
Seyed Mohmmad Tavangar ◽  
Zahra Nozhat ◽  
S Melika Fanaei ◽  
...  

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