Relevance of BRAFV600E Mutation Testing Versus RAS Point Mutations and RET/PTC Rearrangements Evaluation in the Diagnosis of Thyroid Cancer

Rossi, Martina; Buratto, Mattia; Tagliati, Federico; Rossi, Roberta; Lupo, Sabrina; Trasforini, Giorgio; Lanza, Giovanni; Franceschetti, Paola; Bruni, Stefano; Uberti, Ettore C. degli; Zatelli, Maria Chiara

doi:10.1089/thy.2014.0338

Cited by 45 publications

(49 citation statements)

References 27 publications

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“…Commercially available panels include several molecular alterations known to be involved in thyroid oncogenesis, such as BRAF , Ras , RET/PTC , and paired box gene 8/peroxisome proliferator‐activated receptor γ1 ( PAX8‐PPARγ1 ). A recent study by Rossi et al demonstrated that testing for BRAF status predicted malignancy better than testing for RAS and RET/PTC and increased the sensitivity of cytology alone on indeterminate lesions . A study by Capelli and colleagues of 85 inconclusive FNA specimens (SFN/FN and suspicious diagnoses) demonstrated a positive predictive value of 100% for malignancy in the subsequent resection specimen with 100% concordance on BRAF status in the FNA and histologic samples …”

Section: Discussionmentioning

confidence: 99%

Use of BRAF v600e immunocytochemistry on FNA direct smears of papillary thyroid carcinoma

Wobker

Kim

Hackman

et al. 2015

Cancer Cytopathology

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BACKGROUND: Mutations of v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) are identified in almost half of all papillary thyroid carcinomas (PTCs). These mutations are specific for PTC and may confer a worse prognosis. An immunohistochemical (IHC) stain for BRAF is commercially available and has been validated in surgical specimens. Fine-needle aspiration (FNA) is frequently used as a diagnostic tool for risk stratification of thyroid nodules. Therefore, the authors evaluated the performance of immunostaining with the anti-BRAF antibody VE1 on FNA direct smears. METHODS: The authors identified 51 FNA specimens that had subsequent surgical resection specimens with a diagnosis of PTC. BRAF VE1 IHC was performed on the surgical specimens to determine their mutation status. The corresponding direct smears were then stained using the same VE1 stain to assess correlation. RESULTS: Twenty-two of the 46 included surgical specimens were positive for BRAF mutations (47.8%) by IHC, consistent with the published rates. The paired cytologic smears from these cases revealed 65.3% concordance. The overall sensitivity of BRAF staining on cytologic smears was 63.6%, and the specificity was 58.3%. Concordance rates were highest in specimens that were diagnosed as malignant or suspicious for malignancy (75% and 85.7%, respectively). The negative predictive value increased to 77.8% when suspicious for follicular neoplasm/suspicious cases were combined. CONCLUSIONS: Specimens that were malignant or suspicious on FNA were most likely to be BRAF concordant. Limitations to the interpretation of smears included low cellularity and obscuring blood, macrophages, or colloid. With further refinement, it is possible that BRAF immunocytochemistry can be applied prospectively to thyroid FNAs for risk stratification and to reduce false-negative rates. Cancer (Cancer Cytopathol) 2015;123:531-9.

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Section: Discussionmentioning

confidence: 99%

Use of BRAF v600e immunocytochemistry on FNA direct smears of papillary thyroid carcinoma

Wobker

Kim

Hackman

et al. 2015

Cancer Cytopathology

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“…RET/PTC1 is the most common RET/PTC rearrangement and is found in up to 60-70% of PTC cases, whereas RET/PTC3 accounts for 20-30%, and other novel rearrangements for less than 5%. BRAF and RET oncogenic alterations appear to be mutually exclusive but also in this case, a recent study identified the simultaneous presence of these genes (Rossi et al, 2015).…”

Section: Ret/ptc Rearrangements:-mentioning

confidence: 61%

“…Mutation in BRAF or RAS occurs in about 70% of PTCs, suggesting that activation of the MAPK pathway is essential for the onset of carcinogenesis and that the alteration of a single effector is sufficient to cause cell transformation (Song et al, 2015). BRAF andRAS mutations are mutually exclusive (Celestino et al, 2012); however, multiple gene mutations were recently identified in several patients (Rossi et al, 2015). While RET/PTC rearrangements are particularly frequent in children (50-60%), BRAF point mutations are more common in adults than in children (50% vs 0-12%).…”

Section: Gene Mutations Associated With Thyroid Carcinomas:-mentioning

confidence: 99%

Molecular Markers and Thyroid Cancer.

Vuttariello¹,

Chiappetta²

2016

IJAR

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“…Clinical follow-up ranged from 2 to 10 years. Before surgery, all patients underwent US-guided FNAB and aspirates were evaluated for cytology and submitted to BRAFV600E somatic mutation analysis as previously described [25].…”

Section: Patientsmentioning

confidence: 99%

Evaluation of the Role of BRAFV600E Somatic Mutation on Papillary Thyroid Cancer Disease Persistence: A Prospective Study

Damiani¹,

Lupo²,

Rossi³

et al. 2018

Eur Thyroid J

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Background: BRAFV600E (c.1799T>A) somatic mutation evaluation in fine needle aspiration biopsies (FNAB) is a powerful diagnostic tool in the settings of papillary thyroid cancer (PTC). However, its prognostic value is still a matter of great debate and has been addressed mostly in retrospective studies. Objectives: To evaluate whether the somatic BRAFV600E mutation, assessed by direct sequencing in FNAB material of thyroid nodules, may correlate with disease persistence in PTC patients. Study Design: We conducted a prospective cohort study investigating 160 PTC patients previously assessed for the somatic BRAFV600E mutation, and submitted to total thyroidectomy, with a follow-up of 2–10 years. Patients were matched according to somatic BRAFV600E mutation (80 BRAF+ and 80 BRAF– patients) and to the presence (LN+, 40 patients each group) or absence (LN, 40 patients each group) of neck lymphnode metastases. Disease persistence was considered according to basal or TSH-stimulated Thyroglobulin (TG) levels, anti-TG antibodies, neck ultrasound, CT scan where applicable and whole body scan after radioiodine ablation treatment (RAI). Results: The presence of the somatic BRAFV600E mutation did not influence the indication for RAI. None of the enrolled patients showed disease recurrence or died due to disease-related causes. During follow-up, disease persistence did not correlate with the presence of somatic BRAFV600E mutation both in patients submitted to RAI nor in those treated more conservatively. Conclusions: The somatic BRAFV600E mutation does not associate with a worse prognosis in low risk PTC and, in our settings, may not be considered an independent risk factor for disease persistence.

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Relevance of BRAF^V600E Mutation Testing Versus RAS Point Mutations and RET/PTC Rearrangements Evaluation in the Diagnosis of Thyroid Cancer

Abstract: BRAF(V600E) mutation analysis is superior to RAS point mutations and evaluation of RET/PTC rearrangements in the diagnosis of thyroid cancer, even in indeterminate lesions.

Cited by 45 publications

References 27 publications

Use of BRAF v600e immunocytochemistry on FNA direct smears of papillary thyroid carcinoma

Use of BRAF v600e immunocytochemistry on FNA direct smears of papillary thyroid carcinoma

Molecular Markers and Thyroid Cancer.

Evaluation of the Role of <b><i>BRAF</i></b>V600E Somatic Mutation on Papillary Thyroid Cancer Disease Persistence: A Prospective Study

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