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Abstract
The most common point mutation in papillary thyroid carcinoma (PTC), the BRAFV600E, has been associated with more aggressive tumor behavior. Data on the frequency of the BRAFV600E mutation in different age groups in patients with or without history of radiation exposure are quite discordant. In most studies, the adequate control groups were not analyzed, and/or the invasive properties of PTC were not evaluated. The aim of this work is a comparison of the frequency of the BRAFV600E mutant protein expression in radiogenic and sporadic PTCs in similar by age groups of patients, and an assessing of invasive tumor properties. Material and methods. The immunohistochemical (IHC) study included 247 radiogenic PTCs (105 — children ≤14 years, 52 — adolescents 15-
18 years, 91 — adults 19-28 years at the time of surgery) and 138 sporadic PTCs (39 — children, 37 — adolescents, 62 — adults of the indicated age). IHC staining was performed with the anti-BRAF (mutated V600E) antibody (VE1) ab228461 (Abcam). Results. The frequency of mutant BRAFV600E protein expression (thus the BRAFV600E mutation) was significantly lower in the radiogenic PTCs than in the sporadic PTCs (10.5% and 30.4%, p=2,607E‑06); the frequency displayed an age uptrend in both series. Comparison of the BRAFV600Epositive and BRAFV600E-negative PTCs in the radiogenic series revealed
statistically significant differences in the frequencies of most characteristics. The radiogenic BRAFV600E-positive PTCs frequently have typical papillary dominant structure, whereas the BRAFV600Enegative PTCs — solid-trabecular (p=1.12E‑06 and p=0.001, respectively). The frequencies of most indicators of tumor invasiveness in the radiogenic BRAFV600E-positive PTCs were statistically significantly lower than in the BRAFV600E-negative ones. In the sporadic series, the BRAFV600E-positive PTCs did not display differences in the frequencies of most characteristics from those of the BRAFV600E-negative tumors,
or, similarly to the radiogenic series, these were in some instances lower, e.g. lymphatic/vascular invasion (p=7.46E‑06) or N1b metastases (p=0.025). When compared, the BRAFV600E-positive PTCs from the two series (unlike BRAFV600E-negative) did not statistically differ from each other for virtually all characteristics. Conclusions. The BRAFV600E mutation is more common in sporadic than radiogenic PTCs, its frequency increases with patients’ age in both series. As compared to the BRAFV600E-negative PTCs, the BRAFV600E-positive PTCs were characterized by the lower (radiogenic) or similar (sporadic)
invasive properties in patients aged up to 28 years at surgery in both etiological series, indicating that the BRAFV600E mutation does not confer more aggressive disease in young patients with PTC of either etiology.
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