Proteomic identification of new biomarkers and application in thyroid cytology.
OBJECTIVE
To validate proteins identified by proteomics as potentially usable markers in thyroid pathology.


METHODS
Frozen sections of thyroid tumors were manually micro-dissected and proteins extracted. Two-dimensional (2D) gel electrophoresis and subsequent liquid chromatography/mass spectroscopy were performed, and differentially expressed proteins were identified. Validation of candidates for tumor markers (galectin-1, galectin-3, S100C and voltage-dependent anion channel 1 [VDAC1]) was done by immunohistochemistry in 21 cell blocks from fine needle aspiration biopsies (FNAB) and corresponding histology specimens (13 cases).


RESULTS
Galectin-3 was negative in benign lesions and positive in FNAB from papillary carcinoma (5 of 5), follicular variant of papillary carcinoma (1 of 4) and follicular carcinoma (1 of 2). S100C was positive in some benign lesions: hyperplasia (2 of 4), goiter (1 of 3) and follicular adenoma (1 of 3), with predominantly nuclear pattern of staining. S100C was positive in malignant lesions, showing cytoplasmic location. Galectin-1 was negative in benign lesions and positive in follicular carcinoma (1 of 2), papillary carcinoma (2 of 5) and follicular variant of papillary carcinoma (1 of 4). VDAC1 was detected in benign and malignant lesions, showing a strong positivity in follicular carcinomas.


CONCLUSIONS
Immunohistochemical validation of potential markers is a crucial step before clinical application in diagnosis. Galectin-3, galectin-1 and S100C can be used to help in discriminating benign and malignant thyroid lesions.
Torres-Cabala
Carlos
C
Surgical Pathology Section, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. 20892, USA.
Bibbo
Marluce
M
Panizo-Santos
Angel
A
Barazi
Heba
H
Krutzsch
Henry
H
Roberts
David D
DD
Merino
Maria J
MJ
D018263:Adenocarcinoma, Follicular / Q000175:diagnosis*; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000096:biosynthesis; D044963:Biopsy, Fine-Needle; D002277:Carcinoma / Q000175:diagnosis* / Q000378:metabolism; D002291:Carcinoma, Papillary / Q000175:diagnosis*; D002853:Chromatography, Liquid / Q000379:methods; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D037483:Galectin 1 / Q000032:analysis / Q000378:metabolism; D037502:Galectin 3 / Q000032:analysis / Q000378:metabolism; D006042:Goiter / Q000175:diagnosis; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D011237:Predictive Value of Tests; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D009418:S100 Proteins / Q000032:analysis / Q000378:metabolism; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology*; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D050995:Voltage-Dependent Anion Channel 1 / Q000032:analysis / Q000378:metabolism
D014408:Biomarkers, Tumor; D037483:Galectin 1; D037502:Galectin 3; C445499:LGALS1 protein, human; D009418:S100 Proteins; C494762:VDAC1 protein, human; C072337:S100A11 protein, human; D050995:Voltage-Dependent Anion Channel 1