scholarly journals Expression of the Ring Ligase PRAJA2 in Thyroid Cancer

2012 ◽  
Vol 97 (11) ◽  
pp. 4253-4259 ◽  
Author(s):  
Silvia Cantara ◽  
Francesco D'Angeli ◽  
Paolo Toti ◽  
Luca Lignitto ◽  
Maria Grazia Castagna ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
Cultured Cells ◽  
Thyroid Tumor ◽  
Mrna Levels ◽  
Malignant Phenotype ◽  
Hormone Production ◽  
Thyroid Cells ◽  
Mutational Status ◽  
Benign Nodules

Introduction: In thyroid cells, binding of TSH to its receptor increases cAMP levels, sustaining thyrocytes growth and hormone production. The main cAMP effector enzyme is protein kinase A (PKA). Praja2 is a widely expressed RING (Really Interesting New Gene) ligase, which degrades the regulatory subunits of PKA, thus controlling the strength and duration of PKA signaling in response to cAMP. Differentiated thyroid cancer expresses a functional TSH receptor, and its growth and progression are positively regulated by TSH and cAMP signaling. Aim: We aimed to analyze the expression of praja2 in a group of 36 papillary thyroid cancer (PTC), 14 benign nodules, and six anaplastic thyroid cancers (ATC). Methods: We measured praja2 mRNA levels by quantitative RT-PCR and praja2 expression by Western blot and immunohistochemistry. Possible association between praja2 mRNA and the presence of known mutations was evaluated. Results: We found a statistical significant increase of mRNA levels in PTC tissue samples, compared with benign nodules and ATC. In particular, mRNA levels were maximal in differentiated thyroid cancer (PTC), progressively decreasing in more aggressive tumors, ATC having the lowest amount of praja2 mRNA. Accordingly, higher levels of praja2 protein were detected in lysates from PTC, compared with ATC. By immunohistochemistry, in PTC sections we observed a marked increase of cytoplasmic praja2 signal, which significantly decreased in less differentiated thyroid tumors, completely disappearing in ATC. Studies in cultured cells stably expressing RET/PTC1 oncogene or mutant BRAF revealed a direct correlation between praja2 mRNA levels and malignant phenotype of transformed cells. Similar results were obtained using thyroid cancer tissues carrying the same mutations. Conclusions: praja2 is markedly overexpressed in differentiated thyroid cancer, and its levels inversely correlate with the malignant phenotype of the tumor. Thus, praja2 is a novel cancer-related gene whose expression is linked to the histotype and mutational status of the thyroid tumor.

scholarly journals DIAGNOSIS OF ENDOCRINE DISEASE: Thyroglobulin measurement using highly sensitive assays in patients with differentiated thyroid cancer: a clinical position paper

2014 ◽  
Vol 171 (2) ◽  
pp. R33-R46 ◽  
Author(s):  
Luca Giovanella ◽  
Penelope M Clark ◽  
Luca Chiovato ◽  
Leonidas Duntas ◽  
Rossella Elisei ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Clinical Guidelines ◽  
Differentiated Thyroid Cancer ◽  
Clinical Care ◽  
Thyroid Tissue ◽  
Position Paper ◽  
Analytical Sensitivity ◽  
Thyroid Cells ◽  
Highly Sensitive

Differentiated thyroid cancer (DTC) is the most common endocrine cancer and its incidence has increased in recent decades. Initial treatment usually consists of total thyroidectomy followed by ablation of thyroid remnants by iodine-131. As thyroid cells are assumed to be the only source of thyroglobulin (Tg) in the human body, circulating Tg serves as a biochemical marker of persistent or recurrent disease in DTC follow-up. Currently, standard follow-up for DTC comprises Tg measurement and neck ultrasound combined, when indicated, with an additional radioiodine scan. Measurement of Tg after stimulation by endogenous or exogenous TSH is recommended by current clinical guidelines to detect occult disease with a maximum sensitivity due to the suboptimal sensitivity of older Tg assays. However, the development of new highly sensitive Tg assays with improved analytical sensitivity and precision at low concentrations now allows detection of very low Tg concentrations reflecting minimal amounts of thyroid tissue without the need for TSH stimulation. Use of these highly sensitive Tg assays has not yet been incorporated into clinical guidelines but they will, we believe, be used by physicians caring for patients with DTC. The aim of this clinical position paper is, therefore, to offer advice on the various aspects and implications of using these highly sensitive Tg assays in the clinical care of patients with DTC.

scholarly journals Transforming acidic coiled-coil 3 and Aurora-A interact in human thyrocytes and their expression is deregulated in thyroid cancer tissues

2007 ◽  
Vol 14 (3) ◽  
pp. 827-837 ◽  
Author(s):  
Salvatore Ulisse ◽  
Enke Baldini ◽  
Matteo Toller ◽  
Jean-Guy Delcros ◽  
Aurélie Guého ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Thyroid Cancer ◽  
Coiled Coil ◽  
Human Thyroid ◽  
Mrna Levels ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Thyroid Cells ◽  
Cancer Tissues

Aurora-A kinase has recently been shown to be deregulated in thyroid cancer cells and tissues. Among the Aurora-A substrates identified, transforming acidic coiled-coil (TACC3), a member of the TACC family, plays an important role in cell cycle progression and alterations of its expression occur in different cancer tissues. In this study, we demonstrated the expression of the TACC3 gene in normal human thyroid cells (HTU5), and its modulation at both mRNA and protein levels during cell cycle. Its expression was found, with respect to HTU5 cells, unchanged in cells derived from a benign thyroid follicular tumor (HTU42), and significantly reduced in cell lines derived from follicular (FTC-133), papillary (B-CPAP), and anaplastic thyroid carcinomas (CAL-62 and 8305C). Moreover, in 16 differentiated thyroid cancer tissues, TACC3 mRNA levels were found, with respect to normal matched tissues, reduced by twofold in 56% of cases and increased by twofold in 44% of cases. In the same tissues, a correlation between the expression of the TACC3 and Aurora-A mRNAs was observed. TACC3 and Aurora-A interact in vivo in thyroid cells and both proteins localized onto the mitotic structure of thyroid cells. Finally, TACC3 localization on spindle microtubule was no more observed following the inhibition of Aurora kinase activity by VX-680. We propose that Aurora-A and TACC3 interaction is important to control the mitotic spindle organization required for proper chromosome segregation.

B Type RAF Kinase (BRAF) Mutational Status in Metastatic Differentiated Thyroid Cancer

2011 ◽  
Vol 121 (S4) ◽  
pp. S105-S105
Author(s):  
D. Crockett ◽  
J. Bentz ◽  
B. Bentz ◽  
K. Maas
Keyword(s):  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
Raf Kinase ◽  
Mutational Status

scholarly journals Standard immunohistochemistry efficiently screens for anaplastic lymphoma kinase rearrangements in differentiated thyroid cancer

2015 ◽  
Vol 22 (1) ◽  
pp. 55-63 ◽  
Author(s):  
Gahee Park ◽  
Tae Hyuk Kim ◽  
Hae-Ock Lee ◽  
Jung Ah Lim ◽  
Jae-Kyung Won ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Anaplastic Lymphoma Kinase ◽  
Differentiated Thyroid Cancer ◽  
Ectopic Expression ◽  
Practical Method ◽  
Thyroid Tumor ◽  
Anaplastic Lymphoma ◽  
Formalin Fixed Paraffin ◽  
Wide Availability ◽  
Formalin Fixed Paraffin Embedded

The anaplastic lymphoma kinase (ALK) gene is frequently rearranged in various types of cancer and is highly responsive to targeted therapeutics. We developed a system to detect rearrangement of ALK in a large group of Korean thyroid cancer patients. We screened 474 malignant or benign thyroid tumor cases to identify ALK fusions. Expression and translocation of the ALK gene were analyzed by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and digital multiplexed gene expression (DMGE) analysis in formalin-fixed paraffin-embedded tissues. Four cases of rearrangement of ALK were detected by IHC, and these cases were validated with FISH on 189 samples. On the other hand, DMGE analysis using Nanostring detected three out of four IHC-positive cases. Two rearrangements of ALK were striatin (STRN)–ALK fusions, which were identified by 5′ RACE analysis. Rearrangements of ALK were found exclusively in v-raf murine sarcoma viral oncogene homolog B (BRAF) WT papillary carcinomas. Given the wide availability and accuracy of IHC for detecting ectopic expression of ALK in the thyroid, we suggest that IHC-based screening can be a practical method for identifying patients with ALK rearrangements in differentiated thyroid cancer.

scholarly journals Proposal of a New Prognostic Model for Differentiated Thyroid Cancer with TERT Promoter Mutations

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2943
Author(s):  
Jun Park ◽  
Sungjoo Lee ◽  
Jiyun Park ◽  
Hyunju Park ◽  
Chang-Seok Ki ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
Cox Regression ◽  
Term Survival ◽  
Poor Prognostic Factor ◽  
Prognostic System ◽  
Tert Promoter ◽  
Mutational Status ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

The role of telomerase reverse transcriptase (TERT) promoter mutations as an independent poor prognostic factor in differentiated thyroid cancer (DTC) patients is well known, but there is no prognostic system that combines the TERT promoter mutation status with tumor-node-metastasis (TNM) stage to predict cancer-specific survival (CSS). A total of 393 patients with pathologically confirmed DTC after thyroidectomy were enrolled. After incorporating wild-type TERT and mutant TERT with stages I, II, and III/IV of the AJCC TNM system 8th edition (TNM-8), we generated six combinations and calculated 10-year and 15-year CSS and adjusted hazard ratios (HRs) for cancer-related death using Cox regression. Then, a new mortality prediction model termed TNM-8T was derived based on the CSS and HR of each combination in the four groups. Of the 393 patients, there were 27 (6.9%) thyroid cancer-related deaths during a median follow-up of 14 years. Patients with a more advanced stage had a lower survival rate (10-year CSS for TNM-8T stage 1, 2, 3, and 4: 98.7%, 93.5%, 77.3%, and 63.0%, respectively; p < 0.001). TNM-8T showed a better spread of CSS (p < 0.001) than TNM-8 (p = 0.002) in the adjusted survival curves. The C-index for mortality risk predictability was 0.880 (95% CI, 0.665–0.957) in TNM-8T and 0.827 (95% CI, 0.622–0.930) in TNM-8 (p < 0.001). TNM-8T, a new prognostic system that incorporates the TERT mutational status into TNM-8, showed superior predictability to TNM-8 in the long-term survival of DTC patients.

The Clinical Significance of Remnant Thyroid Tissue in Thyroidectomized Differentiated Thyroid Cancer Patients on 131I-SPECT/CT

2021 ◽  
Author(s):  
Feng Wang ◽  
Hui Nie ◽  
Wei Li ◽  
Rusen Zhang ◽  
Wen Li
Keyword(s):  
Risk Factors ◽  
Thyroid Cancer ◽  
Clinical Significance ◽  
Differentiated Thyroid Cancer ◽  
Thyroid Cartilage ◽  
Thyroid Tissue ◽  
Thyroid Tumor ◽  
Chi Square ◽  
Ct Findings ◽  
Remnant Thyroid

Abstract BackgroundTo explore the 131I-SPECT/CT characteristics of remnant thyroid tissue (RTT) in differentiated thyroid cancer (DTC), further assess the risk factors and clinical significance. Methods 52 DTC patients after total thyroidectomy had undergone neck 131I-SPECT/CT before 131I ablation. The diagnosis of RTT was based on SPECT/CT and follow-up at least 3 months. The anatomic locations and features of SPECT/CT of RTT were assessed by reviewers. The risk factors of RTT with CT positive were analyzed by the chi-square test. Results A total of 80 lesions of RTT were diagnosed in this study, most of them were mainly located in the regions adjacent to trachea cartilage (37/80) or lamina of thyroid cartilage(17/80). On SPECT/CT of RTT, low, moderate and high uptake were respectively noted in 10, 24 and 46 lesions, definite positive, suspected positive and negative CT findings were respectively noted in 10, 21 and 49. The RTT lesions with definite positive CT findings were mainly located adjacent to lamina of thyroid cartilage (5/10). Primary thyroid tumor (P=0.029) and T stage (P=0.000) were the effective risk factors of CT positive RTT.Conclusion: RTT has certain characteristic distribution and appearances on SPECT/CT. Most of RTT with definite CT abnormalities located adjacent to lamina of thyroid cartilage, which suggest surgeons should strengthen the careful removal in this region, especially primary thyroid tumor involving bilateral and T4 stage. This study can provide a certain value for the improvement of thyroidectomy quality in DTC patients.

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