Mutações nos tumores da tiróide de indivíduos irradiados na infância por tinea capitis

Na década de 50-60 foi usada a epilação do couro cabeludo através do uso de raios X para o tratamento da tinea capitis (tinha). O estudo destes indivíduos mostrou um aumento da frequência de tumores na zona da cabeça e pescoço, nomeadamente de tumores da tiróide. Tendo tido acesso a uma cohorte tratada desta forma no norte de Portugal, foi realizada uma pesquisa das mutações mais frequentes dos tumores da tiróide (BRAF, NRAS e o rearranjo cromossómico RET/PTC), num grupo de indivíduos desta cohorte que desenvolveram esses tumores. Os resultados mostraram que a frequência da mutação BRAF^V600E nos carcinomas papilares da tiróide é das mais elevadas já descritas em tumores de tiróide de indivíduos irradiados.

Autores e afiliações:

Paula Boaventura¹, Dina Pereira¹, Ricardo Celestino¹, Adélia Mendes¹, Tadao Nakasawa^1,2, José Teixeira-Gomes¹, Manuel Sobrinho-Simões^1,3,4, Paula Soares^1,3,

1 - IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Portugal

2 - Department of Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan

3 - Department of Pathology and Oncology, Medical Faculty, University of Porto, Portugal

4 – Department of Pathology, Hospital Centre of S. João, Porto, Portugal

Abstract:

Objective - Exposure to ionizing radiation at young age is the strongest risk factor for the occurrence of papillary thyroid carcinoma (PTC). RET/PTC rearrangements are the most frequent genetic alterations associated with radiation-induced PTC, whereas BRAF and RAS mutations and PAX8-PPARG rearrangement have been associated with sporadic PTC.  We decided to search for such genetic alterations in PTCs of patients subjected in the childhood to scalp irradiation.

Design - We studied 67 thyroid tumours from 49 individuals irradiated in childhood for tinea capitis scalp epilation: 36 malignant (12 cases of conventional PTC – cPTC, 2 cPTC metastases, 20 cases of follicular variant PTC – FVPTC, one oncocytic variant of PTC and one follicular carcinoma)  and 31 follicular adenomas (FTA).

Methods - The lesions were screened for the BRAF^V600E and NRAS mutations and for RET/PTC and PAX8-PPARG rearrangements.

Results – BRAF^V600E mutation was detected in 7 out of 14 (50%) cPTC and 2 out of 20 FVPTC (10%) (p=0.019). NRAS mutation was present in one case of FVPTC (5%). RET/PTC1 rearrangement was found, by RT-PCR, in one out of 17 cases (5.9%) and by FISH in 2 out of 6 cases (33%).  PAX8-PPARG rearrangement was not detected in any carcinoma. None of the follicular adenomas presented any of the aforementioned genetic alterations.

Conclusions – The prevalence of BRAF^V600E mutation in our series is the highest reported in series of PTCs arising in radiation exposed individuals.  The prevalence of RET/PTC1 rearrangement fits with the values recently described in a similar setting.

Revista:

European Journal of Endocrinology

Link:

http://eje-online.org/content/early/2013/08/21/EJE-13-0543.abstract