Clinicopathological characteristics including <i>BRAF</i> V600E mutation status and PET/CT findings in papillary thyroid carcinoma

Choi, Eun Kyoung; Chong, Ari; Ha, Jung‐Min; Jung, Chan Kwon; O, Joo Hyun; Kim, Sung Hoon

doi:10.1111/cen.13335

Cited by 14 publications

(11 citation statements)

References 28 publications

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“…Although BRAF V600E was not associated with clinicopathological features that predict worse prognosis in this pediatric population, we show here that the BRAF V600E mutation is correlated with larger tumor sizes. Our data corroborate with previous findings in adult PTC, in which this mutation was associated with a larger tumor size …”

Section: Discussionsupporting

confidence: 93%

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AGK‐BRAF is associated with distant metastasis and younger age in pediatric papillary thyroid carcinoma

Sisdelli

Cordioli

Vaisman

et al. 2019

Pediatric Blood & Cancer

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Background The incidence of thyroid carcinoma has increased in most populations, including pediatric patients. The increase is almost exclusively due to an increase in the incidence of papillary thyroid carcinoma (PTC). Genetic alterations leading to mitogen‐activated protein kinase (MAPK) pathway activation are highly prevalent in PTC, with BRAF V600E mutation being the most common event in adult PTC. Although a lower prevalence of BRAF V600E had been reported among pediatric patients, a higher prevalence of BRAF fusion has been identified in both radiation‐exposed and sporadic pediatric PTC. However, little is known about the prognostic implications of BRAF fusions in pediatric PTC. Procedure In this study, we investigated the prevalence of BRAF alterations (AGK‐BRAF fusion and BRAF V600E mutation) in a large set of predominantly sporadic pediatric PTC cases and correlate with clinicopathological features. Somatic AGK‐BRAF fusion was investigated by RT‐PCR and confirmed by FISH break‐apart. The BRAF V600E mutation was screened using Sanger sequencing. Results AGK‐BRAF fusion, found in 19% of pediatric PTC patients, was associated with distant metastasis and younger age. Conversely, the BRAF V600E, found in 15% of pediatric PTC patients, was correlated with older age and larger tumor size. Conclusion Collectively, our results advance knowledge concerning genetic bases of pediatric thyroid carcinoma, with potential implications for diagnosis, prognosis, and therapeutic approaches.

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Section: Discussionsupporting

confidence: 93%

“…Our data corroborate with previous findings in adult PTC, in which this mutation was associated with a larger tumor size. [52][53][54] Although large in size our study is limited by the biases of being a retrospective analysis and not having proper follow-up of all the patients.…”

Section: Discussionmentioning

confidence: 98%

AGK‐BRAF is associated with distant metastasis and younger age in pediatric papillary thyroid carcinoma

Sisdelli

Cordioli

Vaisman

et al. 2019

Pediatric Blood & Cancer

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“…BRAF V600 wild-type melanomas (approximately 50% of melanomas) often have alternative mutations in the MAPK-pathway including RAS or MEK1/2 that are also associated with glycolytic dependency and increased glucose uptake [ 23 – 25 ]. In thyroid carcinoma, BRAF V600E tumours show increased expression of glucose transporter (GLUT) and higher SUVs compared to BRAF V600 wild-type tumours [ 26 , 27 ]. We found no difference in tumour glucose uptake and MATV between patients with and without a BRAF V600 or RAS mutation.…”

Section: Discussionmentioning

confidence: 99%

Mapping heterogeneity in glucose uptake in metastatic melanoma using quantitative 18F-FDG PET/CT analysis

et al. 2018

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BackgroundMetastatic melanoma patients can have durable responses to systemic therapy and even long-term survival. However, a large subgroup of patients does not benefit. Tumour metabolic alterations may well be involved in the efficacy of both targeted and immunotherapy. Knowledge on in vivo tumour glucose uptake and its heterogeneity in metastatic melanoma may aid in upfront patient selection for novel (concomitant) metabolically targeted therapies. The aim of this retrospective study was to provide insight into quantitative 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) parameters and corresponding intra- and inter-patient heterogeneity in tumour 18F-FDG uptake among metastatic melanoma patients. Consecutive, newly diagnosed stage IV melanoma patients with a baseline 18F-FDG PET/CT scan performed between May 2014 and December 2015 and scheduled to start first-line systemic treatment were included. Volume of interests (VOIs) of all visible tumour lesions were delineated using a gradient-based contour method, and standardized uptake values (SUVs), metabolically active tumour volume (MATV) and total lesion glycolysis (TLG) were determined on a per-lesion and per-patient basis. Differences in quantitative PET parameters were explored between patient categories stratified by BRAFV600 and RAS mutational status, baseline serum lactate dehydrogenase (LDH) levels and tumour programmed death-ligand 1 (PD-L1) expression.ResultsIn 64 patients, 1143 lesions ≥ 1 ml were delineated. Median number of lesions ≥ 1 ml was 6 (range 0–168), median maximum SUVpeak 9.5 (range 0–58), median total MATV 29 ml (range 0–2212) and median total TLG 209 (range 0–16,740). Per-patient analysis revealed considerable intra- and inter-patient heterogeneity. Maximum SUVs, MATV, number of lesions and TLG per patient did not differ when stratifying between BRAFV600 or RAS mutational status or PD-L1 expression status, but were higher in the patient group with elevated LDH levels (> 250 U/l) compared to the group with normal LDH levels (P < 0.001). A subset of patients with normal LDH levels also showed above median tumour 18F-FDG uptake.ConclusionsBaseline tumour 18F-FDG uptake in stage IV melanoma is heterogeneous, independent of mutational status and cannot be fully explained by LDH levels. Further investigation of the prognostic and predictive value of quantitative 18F-FDG PET parameters is of interest.Electronic supplementary materialThe online version of this article (10.1186/s13550-018-0453-x) contains supplementary material, which is available to authorized users.

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“…A limited number of studies have investigated the association between FDG-avidity of the tumors with BRAF V600E mutation status and clinicopathological features [13][14][15]. While some studies suggest primary or recurrent tumors bearing BRAF V600E mutation may have higher FDG-avidity [16,17], data on the correlation between other clinicopathological features and FDGavidity are rather sparse. Therefore, we aimed to determine the relationship between clinicopathologic factors, BRAF V600E mutation status and FDG avidity in a rather homogenous group of patients with recurrent or metastatic RAI-negative DTC.…”

Section: Introductionmentioning

confidence: 99%

Relationship between clinicopathologic factors and FDG avidity in radioiodine-negative recurrent or metastatic differentiated thyroid carcinoma

et al. 2021

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Background In this study, we investigated the relationship between clinicopathologic factors, BRAFV600E mutation status and [18F] F-fluoro-2-deoxyglucose (FDG) avidity in patients with radioiodine (RAI)-negative recurrent or metastatic differentiated thyroid cancer (DTC). Methods From 2015 to 2018 all patients with suspected recurrent or metastatic radioiodine-negative DTC patients who underwent FDG positron emission tomography/computed tomography (PET/CT) were retrospectively reviewed. Suspected lesions on FDG PET/CT were biopsied and underwent BRAFV600E mutation testing by immunohistochemistry and real-time PCR. Tumor size, recurrent versus metastatic disease, histopathologic features including classical type versus aggressive subtypes (poorly differentiated, tall cell, columnar cell, hobnail variants) and BRAFV600E mutation status were correlated with the SUVmax of highest hypermetabolic lesions on FDG PET/CT by the univariate analysis using logistic regression. Results Sixty-three consecutive patients, 55 (87.3%) female, with median age of 48 (range 17–81) were included. The majority of patients had BRAFV600E mutation and classical subtype, 55/63 (87.3%) and 45/63(71.4%), respectively. Thyroglobulin at the time of suspected recurrence was 262.7 ng/ml (range 16.3–1000) and patients received a median 3 prior RAI treatments. Fifty-four patients (85.7%) had local recurrence. The majority of patients 58/63 (92.1%) had FDG-avid disease on PET/CT. On univariate analysis, tumor size aggressive histopathologic types and distant metastasis are the significant factors for predicting FDG uptake, p = 0.04, p = 0.001 and p = 0.004 respectively. Although FDG uptake of BRAFV600E bearing recurrent/metastatic RAIR DTC lesions was higher than those without the mutation, the difference did not reach statistical significance, SUVmax of 7.11 versus 4.91, respectively, p = 0.2. Conclusion The majority of recurrent or metastatic RAI-negative DTC have BRAFV600E mutation and detectable disease on FDG PET/CT. FDG avidity of the recurrent or metastatic RAI-negative DTC is independently associated with the aggressive histopathologic features.

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Clinicopathological characteristics including BRAF V600E mutation status and PET/CT findings in papillary thyroid carcinoma

Abstract: Primary tumour size and the BRAF V600E mutation are significant factors associated with the SUVmax on preoperative PET/CT in patients with PTC.

Cited by 14 publications

References 28 publications

AGK‐BRAF is associated with distant metastasis and younger age in pediatric papillary thyroid carcinoma

AGK‐BRAF is associated with distant metastasis and younger age in pediatric papillary thyroid carcinoma

Mapping heterogeneity in glucose uptake in metastatic melanoma using quantitative 18F-FDG PET/CT analysis

Relationship between clinicopathologic factors and FDG avidity in radioiodine-negative recurrent or metastatic differentiated thyroid carcinoma

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