title: BRAF (V600E) associates with cytoplasmatic localization of p27kip1 and higher cytokeratin 19 expression in papillary thyroid carcinoma.
abstract: The genetic alterations are responsible for the altered protein expression in tumors. The knowledge of the link between the altered protein expression and genetic alterations may provide potentially important biological and clinical information. In this study, the expression of some protein markers (Gal-3, p21Kip1, CK19) known to be associated to the papillary thyroid carcinoma (PTC) was assessed in a series of surgical samples by immunohistochemistry, and the association between expression of these markers and the BRAF (V600E) mutation was investigated. Gal-3 positive staining was evident in 26 % of benign nodules. The BRAF (V600E) mutation and Gal-3 expression, were found in 55.5 and 87 % of PTC respectively, and were unlinked. The expression of CK19 in benign nodules was weak and limited to scattered follicular cells. Diffuse cytoplasmatic expression of CK19 was present in malignant tumors in a variable percentage of cells. A higher percentage of CK19 expressing cells was associated with BRAF (V600E) (P ≤ 0.001). All benign nodules displayed nuclear p27kip1 in more than 15 % of the cells. Twenty-nine PTC showed a cytoplasmatic staining with negative nuclei. PTC with cytoplasmatic or 0-5 % of cells with nuclear staining, 6-15 % or >15 % of cells with nuclear staining were 72 (66.7 %), 24 (22.2 %), and 12 (11.1 %) respectively. In BRAF (V600E) positive tumors, the cytoplasmatic localization of p27kip1 was significantly more frequent (P = 0.024). In conclusion, we provide evidences that BRAF (V600E) is non-associated with Gal-3 expression, whereas it is associated with cytoplasmatic localization of p27kip1 and higher CK19 expression in PTC.
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Via Allende, 84081, Baronissi, Salerno, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Guerra
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Marotta
authors.forename: Maurilio
authors.initials: M
authors.lastname: Deandrea
authors.forename: Manuela
authors.initials: M
authors.lastname: Motta
authors.forename: Paolo Piero
authors.initials: PP
authors.lastname: Limone
authors.forename: Alessia
authors.initials: A
authors.lastname: Caleo
authors.forename: Pio
authors.initials: P
authors.lastname: Zeppa
authors.forename: Silvano
authors.initials: S
authors.lastname: Esposito
authors.forename: Franco
authors.initials: F
authors.lastname: Fulciniti
authors.forename: Mario
authors.initials: M
authors.lastname: Vitale
mesh_terms: D019943:Amino Acid Substitution; D002277:Carcinoma / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D002291:Carcinoma, Papillary; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D037502:Galectin 3 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D018698:Glutamic Acid / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D053539:Keratin-19 / Q000378:metabolism*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D014633:Valine / Q000235:genetics
chemical_list: C436291:CDKN1B protein, human; D037502:Galectin 3; D053539:Keratin-19; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018698:Glutamic Acid; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D014633:Valine