Serum CYFRA 21.1 Level Predicts Disease Course in Thyroid Cancer with Distant Metastasis

Abstract

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.

Diagnostic utilities of washout CYFRA 21-1 combined with washout thyroglobulin for metastatic lymph nodes in thyroid cancer: a prospective study

“…The key difference in the present work was the precise matching of preoperatively confirmed metastatic LNs with those evaluated during surgery; this enabled more accurate interpretation of the final pathologies and the washout Tg and CYFRA 21-1 levels. Many studies have suggested that the CYFRA 21-1 level is a useful prognostic factor in patients with various cancers, but most have only measured serum levels of this marker 21 , 22 , 30 , 31 . The washout CYFRA 21-1 levels of LN FNA samples have seldom been assayed; no useful diagnostic/prognostic cutoff has yet been established.…”

“…Several studies have suggested that serum levels of CYFRA 21-1 are prognostic of thyroid cancer progression 21 , 22 . Jeong et al demonstrated the utility of such measurements in thyroid cancer patients with distant metastases who exhibited disease progression 22 .…”

“…When the washout Tg concentration is high but the cytology negative, it is necessary to identify additional tumor markers that support and enhance diagnostic specificity and sensitivity. Cytokeratin fragment 21-1 (CYFRA 21-1) is a soluble fragment of the cytokeratin 19 protein that serves as a biomarker of LN metastasis and cell metastatic potential 21 , 22 . It is a useful diagnostic marker not only of thyroid but also stomach and ovarian cancers, laryngeal squamous cell carcinomas, liver metastases of colorectal cancer, and LN metastases of lung cancer 23 – 29 .…”

“…It is a useful diagnostic marker not only of thyroid but also stomach and ovarian cancers, laryngeal squamous cell carcinomas, liver metastases of colorectal cancer, and LN metastases of lung cancer 23 – 29 . In thyroid cancer, most prior studies have focused on serum levels of this marker 21 , 22 , 30 , 31 ; few works have assayed CYFRA 21-1 concentrations in metastatic LN washouts 27 , 32 . A previous multidisciplinary study in our institution found that a combination of washout CYFRA 21-1 and Tg levels, and FNAC, afforded high sensitivity of 98.8%, highlighting the diagnostic utility of CYFRA 21-1 27 .…”

Development of a Colloidal Gold Immunochromatographic Strip for Rapid Detection of Cyfra 21-1 in Lymph Node Metastasis of Thyroid Cancer

“…Lei et al developed an ICS test based on fluorescent microspheres for the rapid and quantitative detection of urinary Cyfra 21-1, which is in use for the diagnosis and prognostic monitoring of bladder cancer, confirming the reliable application of immunochromatographic technology in detecting Cyfra 21-1 levels ( Lei et al, 2019 ). Recent studies have also shown that an increased Cyfra 21-1 level is associated with distant metastasis and tumor progression of thyroid cancer ( Giovanella et al, 2017 ; Jeong et al, 2021 ). Determination of the Cyfra 21-1 level in the eluent from a fine-needle aspiration of the lymph node may improve the diagnosis of lymph node metastasis in patients with differentiated thyroid cancer ( Lee et al, 2019 ).…”