title: Differential protein expression profiles of cyst fluid from papillary thyroid carcinoma and benign thyroid lesions.
abstract: Cystic papillary thyroid carcinoma (cPTC) is a subgroup of PTC presenting a diagnostic challenge at fine needle aspiration biopsy (FNAB). To further investigate this entity we aimed to characterize protein profiles of cyst fluids from cPTC and benign thyroid cystic lesions. In total, 20 cPTCs and 56 benign thyroid cystic lesions were studied. Profiling by liquid chromatography tandem mass spectrometry (LC-MS/MS) was performed on cyst fluids from a subset of cases after depletion, and selected proteins were further analyzed by Western blot (WB), immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA). A total of 1,581 proteins were detected in cyst fluids, of which 841 were quantified in all samples using LC-MS/MS. Proteins with different expression levels between cPTCs and benign lesions were identified by univariate analysis (41 proteins) and multivariate analysis (59 proteins in an orthogonal partial least squares model). WB analyses of cyst fluid and IHC on corresponding tissue samples confirmed a significant up-regulation of cytokeratin 19 (CK-19/CYFRA 21-1) and S100A13 in cPTC vs. benign lesions. These findings were further confirmed by ELISA in an extended material of non-depleted cyst fluids from cPTCs (n = 17) and benign lesions (n = 55) (p<0.05). Applying a cut-off at >55 ng/ml for CK-19 resulted in 82% specificity and sensitivity. For S100A13 a cut-off at >230 pg/ml revealed a 94% sensitivity, but only 35% specificity. This is the first comprehensive catalogue of the protein content in fluid from thyroid cysts. The up-regulations of CK-19 and S100A13 suggest their possible use in FNAB based preoperative diagnostics of cystic thyroid lesions.
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, SE-171 76, Stockholm, Sweden; Cancer Center Karolinska, Karolinska University Hospital, SE-171 76, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 76, Stockholm, Sweden.
authors.forename: Andrii
authors.initials: A
authors.lastname: Dinets
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, SE-171 76, Stockholm, Sweden; Cancer Proteomics Mass Spectrometry, Science for Life Laboratory, SE-171 65, Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Pernemalm
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 76, Stockholm, Sweden; Cancer Proteomics Mass Spectrometry, Science for Life Laboratory, SE-171 65, Stockholm, Sweden.
authors.forename: Hanna
authors.initials: H
authors.lastname: Kjellin
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, SE-171 76, Stockholm, Sweden; Cancer Center Karolinska, Karolinska University Hospital, SE-171 76, Stockholm, Sweden; Department of Pathology-Cytology, Karolinska University Hospital, SE-171 76, Stockholm, Sweden.
authors.forename: Vitalijs
authors.initials: V
authors.lastname: Sviatoha
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, SE-171 76, Stockholm, Sweden; Cancer Center Karolinska, Karolinska University Hospital, SE-171 76, Stockholm, Sweden.
authors.forename: Anastasios
authors.initials: A
authors.lastname: Sofiadis
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, SE-171 76, Stockholm, Sweden; Cancer Center Karolinska, Karolinska University Hospital, SE-171 76, Stockholm, Sweden; Department of Pathology-Cytology, Karolinska University Hospital, SE-171 76, Stockholm, Sweden.
authors.forename: C Christofer
authors.initials: CC
authors.lastname: Juhlin
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 76, Stockholm, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Zedenius
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, SE-171 76, Stockholm, Sweden; Cancer Center Karolinska, Karolinska University Hospital, SE-171 76, Stockholm, Sweden.
authors.forename: Catharina
authors.initials: C
authors.lastname: Larsson
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, SE-171 76, Stockholm, Sweden; Cancer Proteomics Mass Spectrometry, Science for Life Laboratory, SE-171 65, Stockholm, Sweden.
authors.forename: Janne
authors.initials: J
authors.lastname: Lehtiö
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, SE-171 76, Stockholm, Sweden; Cancer Center Karolinska, Karolinska University Hospital, SE-171 76, Stockholm, Sweden; Department of Pathology-Cytology, Karolinska University Hospital, SE-171 76, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Höög
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002277:Carcinoma / Q000378:metabolism*; D002291:Carcinoma, Papillary; D003560:Cysts / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007525:Isoelectric Focusing; D008297:Male; D008875:Middle Aged; D053719:Tandem Mass Spectrometry; D000077273:Thyroid Cancer, Papillary; D013959:Thyroid Diseases / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism*; D059467:Transcriptome; D055815:Young Adult