Aim of this work is to provide a detailed comparison of clinical-pathologic features between well differentiated and poorly differentiated tumors according to their BRAF and RASSF1A status.We analyzed RASSF1A methylation by MSP and BRAF mutation by LCRT-PCR with LightMix® kit BRAF V600E in neoplastic thyroid tissues. Immunohistochemical evaluation of RASSF1A expression was also performed by standard automated LSAB-HRP technique.An overall higher degree of RASSF1A over-expression than normal thyroid parenchyma surrounding tumors (p<0.05) has been found in all malignant well differentiated lesions. Moreover, statistically significant higher levels of RASSF1A expression were observed in differentiated cancers associated to an inflammatory autoimmune background (p = 0.01). Amplifiable DNA for LC PCR with LightMix® kit BRAF V600E was obtained in 9 PTCs, 4 FVPTCs, 5 ATCs and 1 control. The V600E mutation was found in 13 of 18 (72%) tumors. BRAF was mutated in 6 of 9 (66%) classical PTC, in 2 of 4 (50%) follicular variant PTC and in all ACs (100%). The overall frequency of RASSF1A promoter methylation observed was 20.5% (9 cases out 44). Hypermethylation of RASSF1A in primary tumors was variable according to histotypes ranging from100% (5/5) in ACs to only 12.5% (4/32) in PTCs. We show a correlation between RASSF1A methylation status and RASSF1A protein expression. Finally, we conclude that BRAF V600E mutation and RASSF1A methylation were pathogenetic event restricted to a subgroup of PTC/FVPTCs in early stage and to clinically aggressive ATCs.

BRAF mutation and RASSF1A expression in thyroid carcinoma of southern Italy

FRANCO, Renato;DI DOMENICO, Marina;
2013

Abstract

Aim of this work is to provide a detailed comparison of clinical-pathologic features between well differentiated and poorly differentiated tumors according to their BRAF and RASSF1A status.We analyzed RASSF1A methylation by MSP and BRAF mutation by LCRT-PCR with LightMix® kit BRAF V600E in neoplastic thyroid tissues. Immunohistochemical evaluation of RASSF1A expression was also performed by standard automated LSAB-HRP technique.An overall higher degree of RASSF1A over-expression than normal thyroid parenchyma surrounding tumors (p<0.05) has been found in all malignant well differentiated lesions. Moreover, statistically significant higher levels of RASSF1A expression were observed in differentiated cancers associated to an inflammatory autoimmune background (p = 0.01). Amplifiable DNA for LC PCR with LightMix® kit BRAF V600E was obtained in 9 PTCs, 4 FVPTCs, 5 ATCs and 1 control. The V600E mutation was found in 13 of 18 (72%) tumors. BRAF was mutated in 6 of 9 (66%) classical PTC, in 2 of 4 (50%) follicular variant PTC and in all ACs (100%). The overall frequency of RASSF1A promoter methylation observed was 20.5% (9 cases out 44). Hypermethylation of RASSF1A in primary tumors was variable according to histotypes ranging from100% (5/5) in ACs to only 12.5% (4/32) in PTCs. We show a correlation between RASSF1A methylation status and RASSF1A protein expression. Finally, we conclude that BRAF V600E mutation and RASSF1A methylation were pathogenetic event restricted to a subgroup of PTC/FVPTCs in early stage and to clinically aggressive ATCs.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11591/191449
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