Serum Cyfra 21.1 and galectin-3 protein levels in relation to immunohistochemical cytokeratin 19 and galectin-3 expression in patients with thyroid tumors
- 169 Downloads
The aim of this study was to assess the clinical utility of circulating preoperative Cyfra 21.1 [soluble fragment of cytokeratin (CK) 19] and galectin-3 (gal-3) in patients with thyroid tumors, to compare their serum values with tissue expression and to analyze the prognostic significance of these markers in relation to the clinical status of postsurgical differentiated thyroid carcinoma (DTC) patients.
Concentrations of Cyfra 21.1 and gal-3 were evaluated by immunoassays in sera of 9 healthy subjects, 97 preoperative patients with diverse thyroid tumors (10 FTA, 63 PTC, 11 FTC, 5 PDTC, 4 ATC, 4 LNM) and 25 postoperative DTC patients (14 remissions and 11 metastases).
Low Cyfra 21.1 values were found in all subgroups, but with a tendency toward higher values in poorly differentiated DTC patients. Compared to the control (0.23 ng/mL), serum levels of gal-3 were significantly elevated in patients with thyroid tumors but with overlapping between adenoma (4.16 ng/mL) and carcinoma (3.85, 4.37, 4.64, 6.07 ng/mL for PTC, PDTC, ATC and LNM, respectively). The tissue expression of CK19 and gal-3 was immunohistochemically determined on 45 matched paraffin-embedded sections. Most thyroid carcinomas showed positive CK19 (27/35) and gal-3 immunostaining (31/35), while adenomas were mostly immunonegative (8/10 and 7/10, respectively). However, there was no significant correlation between their serum and tissue levels. Clinical status of postoperative DTC patients had no influence on serum concentrations of the tested markers.
While CK19 and gal-3 are accurate as tissue markers, their serum levels could not be used as reliable markers for identification of thyroid malignancy or in thyroid cancer follow-up. On the other hand, a tendency toward higher serum levels of Cyfra 21.1 in the small number of PDTC patients examined adds weight to previous reports postulating a role for cytokeratins in predicting a high degree of malignancy.
KeywordsCyfra 21.1 Cytokeratin 19 Galectin-3 Thyroid carcinoma Immunohistochemistry Human serum
This research was supported by the Ministry of Science and Technological Development of the Republic of Serbia (project 143039).
Conflict of interest statement
We declare that we have no conflict of interest.
- Bartolazzi A, Gasbarri A, Papotti M, Bussolati G, Lucante T, Khan A, Inohara H, Marandino F, Orlandi F, Nardi F, Vecchione A, Tecce R, Larsson O, Group ThyroidCancerStudy (2001) Application of an immunodiagnostic method for improving preoperative diagnosis of nodular thyroid lesions. Lancet 357:1644–1650CrossRefPubMedGoogle Scholar
- Giovanella L, Ceriani L, Ghelfo A, Maffioli M (2008) Circulating cytokeratin 19 fragments in patients with benign nodules and carcinomas of the thyroid gland. Int J Biol Markers 23:61–64Google Scholar
- Hedinger C, Williams ED, Sobin LH (1988) Histological typing of thyroid tumours. In: International histological classification of tumours. World Health Organization, 2nd edn. Springer, Geneva, pp 1–66Google Scholar
- Inohara H, Segawa T, Miyauchi A, Yoshii T, Nakahara S, Raz A, Maeda M, Miyoshi E, Kinoshita N, Yoshida H, Furukawa M, Takenaka Y, Takamura Y, Ito Y, Taniguchi N (2008) Cytoplasmic and serum gal-3 in diagnosis of thyroid malignancies. Biochem Biophys Res Commun 376:605–610CrossRefPubMedGoogle Scholar
- Orlandi F, Saggiorato E, Pivano G, Puligheddu B, Termine A, Cappia S, De Giuli P, Angeli A (1998) Galectin-3 is a presurgical marker of human thyroid carcinoma. Cancer Res 58:3013–3020Google Scholar
- Sánchez-Carbayo M, Espasa A, Chinchilla V, Herrero E, Megías J, Mira A, Soria F (1999) New electrochemiluminescent immunoassay for the determination of CYFRA 21–1: analytical evaluation and clinical diagnostic performance in urine samples of patients with bladder cancer. Clin Chem 45:1944–1953PubMedGoogle Scholar