title: BRAF mutation and RASSF1A expression in thyroid carcinoma of southern Italy.
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 nine PTCs, four FVPTCs, five ATCs, and one 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.
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Anatomic Pathology, University of Foggia, Foggia, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Santoro
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pannone
authors.forename: Maria Antonia
authors.initials: MA
authors.lastname: Carosi
authors.forename: Arianna
authors.initials: A
authors.lastname: Francesconi
authors.forename: Edoardo
authors.initials: E
authors.lastname: Pescarmona
authors.forename: Giuseppe Maria
authors.initials: GM
authors.lastname: Russo
authors.forename: Antonia
authors.initials: A
authors.lastname: Feola
authors.forename: Simona
authors.initials: S
authors.lastname: Losito
authors.forename: Renato
authors.initials: R
authors.lastname: Franco
authors.forename: Luigi
authors.initials: L
authors.lastname: Nappi
authors.forename: Gabriella
authors.initials: G
authors.lastname: Aquino
authors.forename: Gaetano
authors.initials: G
authors.lastname: De Rosa
authors.forename: Marina
authors.initials: M
authors.lastname: Di Domenico
authors.forename: Pantaleo
authors.initials: P
authors.lastname: Bufo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002291:Carcinoma, Papillary / Q000235:genetics / Q000473:pathology; D019175:DNA Methylation / Q000235:genetics; D003710:Demography; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007558:Italy; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D009691:Nucleic Acid Denaturation; D011401:Promoter Regions, Genetic / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf