Circulating BRAFV600E Levels Correlate with Treatment in Patients with Thyroid Carcinoma
Background: BRAF V600E is the most common mutation in papillary thyroid carcinoma (PTC) and can be associated with aggressive disease. Previously, a highly sensitive blood RNA-based BRAF V600E assay was reported. The objective of this study was to assess the correlation of BRAF V600E circulating tum...
Gespeichert in:
Veröffentlicht in: | Thyroid (New York, N.Y.) N.Y.), 2018-03, Vol.28 (3), p.328-339 |
---|---|
Hauptverfasser: | , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | Background:
BRAF
V600E
is the most common mutation in papillary thyroid carcinoma (PTC) and can be associated with aggressive disease. Previously, a highly sensitive blood RNA-based
BRAF
V600E
assay was reported. The objective of this study was to assess the correlation of
BRAF
V600E
circulating tumor RNA levels with surgical and medical treatment.
Methods:
Circulating
BRAF
V600E
levels were assessed in (i) a murine model of undifferentiated (anaplastic) thyroid carcinoma with known
BRAF
V600E
mutation undergoing
BRAF
V600E
-inhibitor (
BRAFi
) treatment, and (ii) in 111 patients enrolled prior to thyroidectomy (
n
= 86) or treatment of advanced recurrent or metastatic PTC (
n
= 25). Blood samples were drawn for
BRAF
V600E
analysis before and after treatment. Testing characteristics were assessed and positivity criteria optimized. Changes in blood
BRAF
V600E
values were assessed and compared to clinical characteristics and response to therapy.
Results:
In a murine model of anaplastic thyroid carcinoma with
BRAF
V600E
mutation, blood
BRAF
V600E
RNA correlated with tumor volume in animals treated with
BRAFi
. In tissue
BRAF
V600E
-positive (
n
= 36) patients undergoing initial surgery for PTC, blood
BRAF
V600E
levels declined postoperatively (median 370.0–178.5 fg/ng;
p
= 0.002). In four patients with metastatic or poorly differentiated thyroid carcinoma receiving targeted therapies, blood
BRAF
V600E
declined following therapy and corresponded with radiographic evidence of partial response or stable disease.
Conclusions:
This study shows the correlation of blood
BRAF
V600E
levels in response to treatment in both an established animal model of thyroid cancer and in patients with
BRAF
V600E
-positive tumors with all stages of disease. This assay represents an alternative biomarker in patients with positive thyroglobulin antibodies, and tumors, which do not express thyroglobulin. |
---|---|
ISSN: | 1050-7256 1557-9077 |
DOI: | 10.1089/thy.2017.0322 |