Stomatin-like protein 2 overexpression in papillary thyroid carcinoma is significantly associated with high-risk clinicopathological parameters and BRAFV600E mutation

Apmis ◽  
2016 ◽  
Vol 124 (4) ◽  
pp. 271-277 ◽  
Author(s):  
Aleksandar Bartolome ◽  
Srdjan Boskovic ◽  
Ivan Paunovic ◽  
Vesna Bozic ◽  
Dubravka Cvejic
Keyword(s):  
High Risk ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Clinicopathological Parameters ◽  
Papillary Thyroid ◽  
Brafv600e Mutation

scholarly journals The ratio of BRAFV600E alleles can be used to assess the biological behavior of papillary thyroid carcinoma

2020 ◽  
Author(s):  
Dingcun Luo ◽  
Yeqin Ni ◽  
Shirong Zhang ◽  
Yanping Xun ◽  
Pan Zhao ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Tumor Recurrence ◽  
Recurrence Risk ◽  
Tumor Stage ◽  
Biological Behavior ◽  
Clinicopathological Parameters ◽  
Quantitative Detection ◽  
Papillary Thyroid ◽  
Brafv600e Mutation

ABSTRACTBackgroundThe BRAFV600E mutations is an important molecular event in the occurrence and development of papillary thyroid carcinoma (PTC). A qualitative detection of the BRAFV600E mutation is still insufficient to explain the biological behavior of PTC. Though quantitative detection of the BRAFV600E mutation can reflect certain characteristics of PTC, its clinical value is still controversial. We aimed to investigate the association between the ratio of BRAFV600E alleles and clinicopathological parameters in PTC patients.MethodsGenomic DNA was extracted from specimens obtained from 329 PTC patients undergoing thyroidectomy. The ratio of BRAFV600E alleles was determined by amplification refractory mutation system (ARMS) and droplet digital polymerase chain reaction (ddPCR). Inconsistent results were further verified by next-generation sequencing (NGS). The clinicopathologic features, clinical tumor stage, and tumor recurrence risk stratification of all patients were correlated with the ratio of BRAFV600E alleles.ResultsThe sensitivity of ddPCR was superior to that of ARMS and almost the same as that of NGS. In total, 275 of 329 patients had the BRAFV600E mutation as determined by ARMS, ddPCR and NGS. The ratio of BRAFV600E alleles ranged from 0.17%-48.0%, with a median ratio of 12.58%, and significantly correlated with tumor size (p<0.001), capsule or extrathyroidal invasion (p<0.001), the number or rate of lymph node metastases (p<0.001), tumor stage (p=0.006) and tumor recurrence risk (p<0.001) but not with sex, age or multifocality. The ratio of BRAFV600E alleles was much lower in PTC patients with Hashimoto’s thyroiditis than in those without (p<0.001).ConclusionsThe ratio of BRAFV600E alleles can reliably reflect the biological behavior of PTC, making it a molecular-based stratification index of recurrence risk. The quantitative detection of BRAFV600E has the potential to guide the clinical diagnosis and treatment of PTC.

scholarly journals Coexistence of BRAFV600E mutation and EGFR overexpression is highly associated with adverse clinicopathological features of papillary thyroid carcinoma

2020 ◽  
Vol 72 (1) ◽  
pp. 37-44
Author(s):  
Ivan Paunovic ◽  
Sonja Selemetjev ◽  
Tijana Isic-Dencic ◽  
Ilona Djoric ◽  
Jelena Jankovic-Miljus ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Expression Profiles ◽  
Growth Factor Receptor ◽  
Molecular Therapy ◽  
Braf V600e ◽  
Clinicopathological Parameters ◽  
Papillary Thyroid ◽  
Brafv600e Mutation ◽  
Tissue Samples

Papillary thyroid carcinoma (PTC) generally has a good prognosis, but in a subset of patients it progresses to aggressive forms. Analysis of molecular alterations in relation to clinical phenotype may help in risk stratification of patients by predicting tumor aggressiveness. We analyzed the expression profiles of epidermal growth factor receptor (EGFR) using immunohistochemistry and the presence of BRAF(V600E) mutation by mutant allele-specific PCR in PTC tissue samples (n=92) in relation to clinicopathological parameters. BRAFV600E was detected in 46.7% of patients and correlated with the presence of lymph node metastasis (LNM, p=0.035) and extrathyroid invasion (EI, p<0.0001). EGFR overexpression was detected in 52.2% of the patients and also correlated with LNM (p<0.0001) and EI (p=0.027). Among patients with a single alteration, the presence of BRAFV600E impacted EI, while EGFR overexpression alone had a greater impact on LNM. The strongest association with adverse features was found in PTC patients with coexisting BRAFV600E and EGFR overexpression (28.3%), among whom LNM and EI were evident in 73% and 69%, respectively (p<0.0001, for both). Thus, the coexistence of BRAFV600E mutation and EGFR overexpression identifies high-risk PTC patients, who should be considered for combined molecular therapy offering a better long-term therapeutic outcome.

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.

Aggressive Papillary Thyroid Carcinoma without Brafv600e Mutation

2014 ◽  
Vol 2 (4) ◽  
Author(s):  
Emine Demirbaş ◽  
Mehmet Aşık ◽  
Semra Özdemir ◽  
Hacer Şen ◽  
Fahri Güneş ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Papillary Thyroid ◽  
Brafv600e Mutation

BRAFV600E MUTATION IN PAPILLARY THYROID CARCINOMA. CLINICAL AND METHODOLOGICAL ASPECTS

2019 ◽  
Vol 65 (1) ◽  
pp. 16-26
Author(s):  
Pavel Rumyantsev ◽  
Petr Nikiforovich ◽  
Andrey Poloznikov ◽  
Andrey Abrosimov ◽  
Vladimir Saenko ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Kinase Inhibitors ◽  
Anaplastic Carcinoma ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Brafv600e Mutation ◽  
Wide Range ◽  
Methodological Aspects

Mutation BRAFV600E is highly specific for papillary thyroid carcinoma. It’s detected in 40-70% of all papillary thyroid carcinoma cases. Moreover this mutation is noticed in anaplastic carcinoma in 40-50%.This fact gives a chance to select patients and provide targeted therapy with multi-kinase inhibitors in cases of unresectable anaplastic carcinoma. The influence of BRAF V600E mutation for response to radioactive iodine therapy requires more evidence-based research. Existing methods for determining the BRAFV600E mutation have different accuracy, availability and cost. Other methodological aspects are also associated with the sample preparation of biological material, the quality of reagents, and the cross-validation of research results. In this review, on the basis of our own experience and literature data, the indications for determining the mutation of the BRAFV600E gene in clinical practice are refined, and a comprehensive comparative analysis of modern research methods has been conducted. This review is focused on a wide range of specialists of different types: oncologists, endocrinologists, radiologists, pathologists, and biologists.

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 Microcalcifications without a thyroid nodule as the sole sign of papillary thyroid carcinoma

2021 ◽  
Vol 2021 ◽  
Author(s):  
Stamatina Ioakim ◽  
Vasilis Constantinides ◽  
Meropi Toumba ◽  
Theodoros Lyssiotis ◽  
Angelos Kyriacou
Keyword(s):  
High Risk ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Gland ◽  
Thyroid Carcinoma ◽  
Histopathological Examination ◽  
Needle Aspiration ◽  
List Type ◽  
Papillary Thyroid ◽  
Resected Tissue ◽  
Current Guidelines

Summary Our objective is to demonstrate the importance of considering microcalcifications even without evidence of nodules as a potential sign of malignancy. Current guidelines, such as those of the British Thyroid Association, acknowledge the clinical significance of microcalcifications only when found within nodules. In this case, they are considered a suspicious feature, classifying the nodules as U5 (i.e. high risk) where fine-needle aspiration biopsy (FNAB) is warranted, following the high likelihood of cancer in these nodules. In addition, there is a dearth of evidence of ultrasound scan (USS) detection of microcalcifications in the thyroid gland outside of nodules, along with their associated clinical implications. Yet, this clinical manifestation is not so infrequent considering that we do encounter patients in the clinic showing these findings upon ultrasound examination. Three patients who presented to our clinic with thyroid-related symptoms were shown to have areas of microcalcifications without a nodule upon sonographic evaluation of their thyroid gland. These incidentally detected hyperechoic foci were later confirmed to correspond to areas of papillary thyroid carcinoma (PTC) on histopathological examination of resected tissue following thyroidectomy. Four more cases were identified with sonographic evidence of microcalcifications without nodules and given their clinical and other sonographic characteristics were managed with active surveillance instead. Learning points Echogenic foci known as microcalcifications may be visible without apparent association to nodular structures. Microcalcifications without nodules may not be an infrequent finding. Microcalcifications are frequently indicative of malignancy within the thyroid gland even without a clearly delineated nodule. Empirically, the usual guidelines for the management of thyroid nodules can be applied to the management of microcalcifications not confined to a nodule, but such a finding per se should be classified as a ‘high-risk’ sign.

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