Proteomic study of thyroid tumors reveals frequent up-regulation of the Ca2+ -binding protein S100A6 in papillary thyroid carcinoma.
BACKGROUND
The accurate diagnosis of thyroid tumors is challenging. Proteomics has emerged as a promising approach for the discovery of molecular diagnostic markers as a potential complement to routine diagnostics.


METHODS
Protein fractions from 29 frozen thyroid tumor tissue samples (10 papillary carcinomas, 9 follicular carcinomas, and 10 follicular adenomas) as well as from normal thyroid tissue were analyzed by surface enhanced laser desorption/ionization time-of-flight mass spectrometry followed by validation by Western blotting and immunohistochemistry.


RESULTS
A Ca2+ binding protein belonging to the S100 family, S100A6, was differentially expressed between papillary and follicular thyroid tumors. Moreover, two posttranslationally modified forms of S100A6 were observed and verified by liquid chromatography-coupled tandem mass spectrometry. Validation by Western blotting displayed a significantly higher expression of S100A6 in papillary thyroid carcinoma (PTC) in comparison with the other tumor groups or normal tissue (p < 0.05). Immunohistochemical analysis on 98 tumors showed that PTC cases had a significantly stronger cytosolic staining and a larger proportion of stained nuclei than follicular tumors. BRAF gene mutation was not significantly associated with S100A6 protein levels.


CONCLUSIONS
This study supports a role of S100A6 in thyroid tumorigenesis and as a potential aid in the discrimination between follicular thyroid tumors and PTC.
Sofiadis
Anastasios
A
Section of Medical Genetics, Karolinska University Hospital, Stockholm, Sweden. Anastasios.Sofiadis@ki.se
Dinets
Andrii
A
Orre
Lukas M
LM
Branca
Rui M
RM
Juhlin
Carl Christofer
CC
Foukakis
Theodoros
T
Wallin
Göran
G
Höög
Anders
A
Hulchiy
Mykola
M
Zedenius
Jan
J
Larsson
Catharina
C
Lehtiö
Janne
J
D018263:Adenocarcinoma, Follicular / Q000235:genetics; D002291:Carcinoma, Papillary / Q000175:diagnosis / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D011499:Protein Processing, Post-Translational; D040901:Proteomics; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins / Q000096:biosynthesis / Q000235:genetics*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry; D013961:Thyroid Gland / Q000528:radiation effects; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000235:genetics*; D015854:Up-Regulation
D018797:Cell Cycle Proteins; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins; C055351:S100A6 protein, human