Abstract
Simple SummaryThe role of serum Cyfra 21.1 as a biomarker in thyroid cancer has yet to be validated. This study investigated the diagnostic or prognostic role of serum Cyfra 21.1 in thyroid cancer. In the present analysis, we found that serum Cyfra 21.1 was increased in thyroid cancer with distant metastasis compared with thyroid cancer without metastasis. Furthermore, in progressive disease when thyroglobulin was undetectable or thyroglobulin monitoring was useless because of thyroglobulin antibody, serial follow-up based on serum Cyfra 21.1 levels might be used as an alternative biomarker for disease monitoring.Background: Serum Cyfra 21.1, the soluble fragment of CK19, has been used as a prognostic tumor marker in various cancers, indicating poor tumor differentiation and increased metastasis. Methods: We analyzed the serum Cyfra 21.1 level in 51 consecutive patients with thyroid cancer manifesting distant metastasis treated with prior total thyroidectomy. Serum Cyfra 21.1 levels of 26 thyroid cancer patients without metastasis and 50 healthy individuals were used for comparison. Results: Higher serum Cyfra 21.1 levels were detected in thyroid cancer patients with distant metastasis compared with healthy subjects and thyroid cancer patients without metastasis (p = 0.012). Serum Cyfra 21.1 levels were significantly increased in patients with positive BRAF V600E mutation (p = 0.019), undergoing Tyrosine Kinase Inhibitor (TKI) therapy (p = 0.008), with radioiodine-refractory status (p = 0.047), and in disease progression compared with those manifesting stable disease (p = 0.007). In progressive disease with undetectable or unmonitored thyroglobulin because of thyroglobulin antibody, serum Cyfra 21.1 was useful as a biomarker for follow-up of disease course. Conclusion: Serum Cyfra 21.1 in thyroid cancer patients might represent an alternative biomarker predicting tumor progression, especially in cases not associated with serum Tg levels.
Highlights
Cytokeratin 19 (CK19) is the lowest molecular weight (40 kDa) member belonging to the cytokeratin family of proteins and contributes to the structural rigidity in simple epithelia and basal layer of most glandular and squamous epithelia in normal tissue [1].CK19 immunostaining is used as a screening marker for neoplasm of epithelial origin because of its wide distribution in many epithelial tissues [2,3,4]
We calculated the receiver operator characteristic (ROC) curve to know the cut-off level of Cyfra 21.1 as a diagnostic test looking for distant metastases in thyroid cancer
We postulate at the timeincreased of metastasis, the cleavage of CK19 tained from fine-needle aspiration werethat significantly in metastatic by caspase 3 resulted in increased synthesis and elevation in serum levels of Cyfra 21.1
Summary
Cytokeratin 19 (CK19) is the lowest molecular weight (40 kDa) member belonging to the cytokeratin family of proteins and contributes to the structural rigidity in simple epithelia and basal layer of most glandular and squamous epithelia in normal tissue [1].CK19 immunostaining is used as a screening marker for neoplasm of epithelial origin because of its wide distribution in many epithelial tissues [2,3,4]. CK19 is highly expressed in differentiated thyroid cancer (DTC), but not in benign thyroid tumors [5,6,7]. Cyfra 21.1 is a soluble fragment of CK19. The prognostic value of serum Cyfra 21.1 has been shown in cancers of breast, lung, bladder, and pancreas [8,9,10,11]. Previous studies have shown that an increased serum Cyfra 21.1 level reflects poorer tumor differentiation and additional metastasis in hepatocellular carcinoma [12] and in lung cancer [13]. The role of serum Cyfra 21.1 as a biomarker in thyroid cancer has yet to be validated. Serum Cyfra 21.1, the soluble fragment of CK19, has been used as a prognostic tumor marker in various cancers, indicating poor tumor differentiation and increased metastasis
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