scholarly journals 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

2006 ◽  
Vol 13 (1) ◽  
pp. 257-269 ◽  
Author(s):  
G Riesco-Eizaguirre ◽  
P Gutiérrez-Martínez ◽  
M A García-Cabezas ◽  
M Nistal ◽  
P Santisteban
Keyword(s):  
High Risk ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Prognostic Impact ◽  
Erk Pathway ◽  
Papillary Thyroid ◽  
Thyroid Cells ◽  
Genetic Event ◽  
Total Body

The oncogene BRAFV600E is the most frequent genetic event in papillary thyroid carcinoma (PTC) but its prognostic impact still remains to be elucidated. We evaluated a representative series of 67 individuals with PTC who underwent total thyroidectomy. BRAF-positive tumours correlated with early recurrences (32% vs 7.6%; P=0.02) during a median postoperative follow-up period of 3 years. Interestingly, within the recurrences, a significant majority had negative radioiodine (131I) total body scans, predicting a poorer outcome as treatment with 131I is not effective. This last observation led us to investigate the role of BRAFV600E and the MEK-ERK pathway in thyroid dedifferentiation, particularly in Na+/I− symporter (NIS) impairment, as this thyroid-specific plasma membrane glycoprotein mediates active transport of I− into the thyroid follicular cells. A subset of 60 PTC samples was evaluated for NIS immunoreactivity and, accordingly, we confirmed a significant low NIS expression and impaired targeting to membranes in BRAF-positive samples (3.5% vs 30%; P=0.005). Furthermore, experiments with differentiated PCCl3 thyroid cells demonstrated that transient expression of BRAFV600E sharply impaired both NIS expression and targeting to membrane and, surprisingly, this impairment was not totally dependent on the MEK-ERK pathway. We have concluded that BRAFV600E is a new prognostic factor in PTC that correlates with a high risk of recurrences and less differentiated tumours due to the loss of NIS-mediated 131I uptake.

scholarly journals The Role of m6A RNA Methylation-Related lncRNAs in the Prognosis and Tumor Immune Microenvironment of Papillary Thyroid Carcinoma

2022 ◽  
Vol 9 ◽  
Author(s):  
Wenlong Wang ◽  
Cong Shen ◽  
Yunzhe Zhao ◽  
Botao Sun ◽  
Xiangyuan Qiu ◽  
...  
Keyword(s):  
High Risk ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Risk Score ◽  
Critical Role ◽  
Clinical Samples ◽  
Papillary Thyroid ◽  
Rna Methylation ◽  
M6a Rna Methylation

Emerging evidence has indicated that N6-methylandenosine (m6A) RNA methylation plays a critical role in cancer development. However, the function of m6A RNA methylation-related long noncoding RNAs (m6A-lncRNAs) in papillary thyroid carcinoma (PTC) has never been reported. This study aimed to investigate the role of m6A-lncRNAs in the prognosis and tumor microenvironment (TME) of PTC. Three subgroups (clusters 1, 2, and 3) were identified by consensus clustering of 19 prognosis-related m6A-lncRNA regulators, of which cluster 1 is preferentially related to unfavorable prognosis, lower immune scores, and distinct immune infiltrate level. A risk-score model was established based on 8 prognosis-related m6A-lncRNAs. Patients with a high-risk score showed a worse prognosis, and the ROC indicated a reliable prediction performance for patients with PTC (AUC = 0.802). As expected, the immune scores, the infiltration levels of immune cells, and ESTIMATE scores in the low-risk subgroups were notably higher (p < 0.001) when compared with those in high-risk subgroups. Furthermore, GSEA analysis revealed that tumor associated pathways, hallmarks, and biological processes were remarkably enriched in the high-risk subgroup. Further analysis indicated that the risk score and age were independent prognostic factors for PTC. An integrated nomogram was constructed that accurately predicted the survival status (AUC = 0.963). Moreover, a lncRNA–miRNA–mRNA regulated network was established based on seven prognosis-related m6A-lncRNAs. In addition, 30 clinical samples and different PTC cells were validated. This is the first study to reveal that m6A-lncRNAs plays a vital role in the prognosis and TME of PTC. To a certain degree, m6A-lncRNAs can be considered as new, promising prognostic biomarkers and treatment targets.

scholarly journals Clinical Significance and Prognostic Impact of Subcutaneous or Intrastrap Muscular Recurrence of Papillary Thyroid Carcinoma

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Yasuhiro Ito ◽  
Mitsuyoshi Hirokawa ◽  
Takuya Higashiyama ◽  
Yuuki Takamura ◽  
Kaoru Kobayashi ◽  
...  
Keyword(s):  
High Risk ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Clinical Significance ◽  
Rare Event ◽  
Distant Recurrence ◽  
Clinicopathological Features ◽  
Prognostic Impact ◽  
Papillary Thyroid ◽  
Initial Surgery

Subcutaneous or intrastrap muscular (SIM) recurrence is rare in papillary thyroid carcinoma (PTC) patients, and its clinical significance remains unclear. We analyzed 29 patients with PTC who showed SIM recurrence in order to elucidate this issue. The incidence of patient age 55 years or older at initial surgery, extrathyroid extension, and clinically detected lymph node metastasis was 83%, 35%, and 46%, respectively. After surgical dissection, 17% of patients showed repeated SIM recurrence. Distant recurrence was detected in 45% of patients and was more likely to occur in patients with high-risk clinicopathological features. In all but one patient in this series, distant recurrence was detected at the same time or after the detection of SIM recurrence. Three patients died of PTC, but none of these patients died of the development of recurrent SIM lesions. These findings suggest that although SIM recurrence is a rare event and is not fatal, it is a predictor of distant recurrence especially in patients with high-risk clinicopathological features. Careful followup is recommended for such patients.

Papillary Thyroid Carcinoma: How Radical Lymphadenectomy Should be Performed?

Swiss Surgery ◽  
2003 ◽  
Vol 9 (2) ◽  
pp. 63-68
Author(s):  
Schweizer ◽  
Seifert ◽  
Gemsenjäger
Keyword(s):  
High Risk ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Low Risk ◽  
Papillary Thyroid ◽  
Sentinel Nodes ◽  
Fand Sich ◽  
Radical Lymphadenectomy ◽  
N Status

Fragestellung: Die Bedeutung von Lymphknotenbefall bei papillärem Schilddrüsenkarzinom und die optimale Lymphknotenchirurgie werden kontrovers beurteilt. Methodik: Retrospektive Langzeitstudie eines Operateurs (n = 159), prospektive Dokumentation, Nachkontrolle 1-27 (x = 8) Jahre, Untersuchung mit Bezug auf Lymphknotenbefall. Resultate: Staging. Bei 42 Patienten wurde wegen makroskopischem Lymphknotenbefall (cN1) eine therapeutische Lymphadenektomie durchgeführt, mit pN1 Status bei 41 (98%) Patienten. Unter 117 Patienten ohne Anhalt für Lymphknotenbefall (cN0) fand sich okkulter Befall bei 5/29 (17%) Patienten mit elektiver (prophylaktischer) Lymphadenektomie, und bei 2/88 (2.3%) Patienten ohne Lymphadenektomie (metachroner Befall) (p < 0.005). Lymphknotenrezidive traten (1-5 Jahre nach kurativer Primärtherapie) bei 5/42 (12%) pN1 und bei 3/114 (2.6%) cN0, pN0 Tumoren auf (p = 0009). Das 20-Jahres-Überleben war bei TNM I + II (low risk) Patienten 100%, d.h. unabhängig vom N Status; pN1 vs. pN0, cN0 beeinflusste das Überleben ungünstig bei high risk (>= 45-jährige) Patienten (50% vs. 86%; p = 0.03). Diskussion: Der makroskopische intraoperative Lymphknotenbefund (cN) hat Bedeutung: - Befall ist meistens richtig positiv (pN1) und erfordert eine ausreichend radikale, d.h. systematische, kompartiment-orientierte Lymphadenektomie (Mikrodissektion) zur Verhütung von - kurablem oder gefährlichem - Rezidiv. - Okkulter Befall bei unauffälligen Lymphknoten führt selten zum klinischen Rezidiv und beeinflusst das Überleben nicht. Wir empfehlen eine weniger radikale (sampling), nur zentrale prophylaktische Lymphadenektomie, ohne Risiko von chirurgischer Morbidität. Ein empfindlicherer Nachweis von okkultem Befund (Immunhistochemie, Schnellschnitt von sampling Gewebe oder sentinel nodes) erscheint nicht rational. Bei pN0, cN0 Befund kommen Verzicht auf 131I Prophylaxe und eine weniger intensive Nachsorge in Frage.

Challenges in the correct assessment of a case of aggressive thyroid carcinoma with synchronous breast cancer, case report and review of the literature: essential role of radiopharmaceuticals

2020 ◽  
Vol 13 ◽  
Author(s):  
Andra Piciu ◽  
Alexandru Mester ◽  
George Rusu ◽  
Doina Piciu
Keyword(s):  
Breast Cancer ◽  
Papillary Thyroid Carcinoma ◽  
Breast Carcinoma ◽  
Thyroid Carcinoma ◽  
Bone Metastases ◽  
Essential Role ◽  
Papillary Thyroid ◽  
Invasive Ductal Breast Carcinoma ◽  
Ductal Breast Carcinoma

Background: Thyroid carcinoma represents a complex pathology that can still be considered a medical challenge, despite having a better prognosis and life expectancy than most other neoplasms, also the scenario of multiple malignancies involving thyroid cancer is nowadays a common reality. Materials and methods: We reviewed the literature regarding the aggressive presentation of synchronous thyroid and breast cancer. In the current paper we are reporting the case of a 59 years-old woman, diagnosed with invasive ductal breast carcinoma and papillary thyroid carcinoma, presenting a natural history of both aggressive synchronous tumors. At the moment of hospitalization, the diagnostic was breast carcinoma with multiple secondary lesions, suggestive for lung and bone metastases, and nodular goiter. Results: Searching the literature PUBMED with the terms “thyroid carcinoma and synchronous breast carcinoma we found 86 studies; introducing the term “aggressive” the result included 4 studies, among them none being relevant for aggressive and synchronous. A similar search was done in SCOPUS finding 92 documents and after introducing the term aggressive, the number of papers was 8, none being for the synchronous aggressive metastatic thyroid and breast carcinoma. The majority of imaging diagnostic tools were used in this particular medical case, in order to ensure the best potential outcome. The final diagnostic was papillary thyroid carcinoma with lung and unusual multiple bone metastases and synchronous invasive ductal breast carcinoma with subcutaneous metastases. Conclusion: The case illustrates the challenges in correct assessment of oncologic patients, despite the advances in medical imaging and technologies and underlines the essential role of nuclear medicine procedures in the diagnostic and therapy protocols.

scholarly journals Analysis of the Role of FRMD5 in the Biology of Papillary Thyroid Carcinoma

2021 ◽  
Vol 22 (13) ◽  
pp. 6726
Author(s):  
Agata M. Gaweł ◽  
Maciej Ratajczak ◽  
Ewa Gajda ◽  
Małgorzata Grzanka ◽  
Agnieszka Paziewska ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Endocrine System ◽  
Metastatic Potential ◽  
Multidrug Resistant ◽  
Thyroid Tumor ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Spheroid Formation

Background: Thyroid carcinoma (TC) is the most common endocrine system malignancy, and papillary thyroid carcinoma (PTC) accounts for >80% of all TC cases. Nevertheless, PTC pathogenesis is still not fully understood. The aim of the study was to elucidate the role of the FRMD5 protein in the regulation of biological pathways associated with the development of PTC. We imply that the presence of certain genetic aberrations (e.g., BRAF V600E mutation) is associated with the activity of FRMD5. Methods: The studies were conducted on TPC1 and BCPAP (BRAF V600E) model PTC-derived cells. Transfection with siRNA was used to deplete the expression of FRMD5. The mRNA expression and protein yield were evaluated using RT-qPCR and Western blot techniques. Proliferation, migration, invasiveness, adhesion, spheroid formation, and survival tests were performed. RNA sequencing and phospho-kinase proteome profiling were used to assess signaling pathways associated with the FRMD5 expressional status. Results: The obtained data indicate that the expression of FRMD5 is significantly enhanced in BRAF V600E tumor specimens and cells. It was observed that a drop in intracellular yield of FRMD5 results in significant alternations in the migration, invasiveness, adhesion, and spheroid formation potential of PTC-derived cells. Importantly, significant divergences in the effect of FRMD5 depletion in both BRAF-wt and BRAF-mutated PTC cells were observed. It was also found that knockdown of FRMD5 significantly alters the expression of multidrug resistant genes. Conclusions: This is the first report highlighting the importance of the FRMD5 protein in the biology of PTCs. The results suggest that the FRMD5 protein can play an important role in controlling the metastatic potential and multidrug resistance of thyroid tumor cells.

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