Serum Cytokeratin 19 Fragment Antigen 21-1 as a Diagnostic and Prognostic Biomarker for Thymic Carcinoma in Thymic Masses

OBJECTIVES: The accurate differentiation of thymic masses, particularly thymic carcinoma (TC), is imperative for guiding optimal treatment selection. This study investigated potential non-invasive biomarkers for discerning thymic malignancies and evaluated their clinical applicability. METHODS: Clinicopathological data from 1897 patients who underwent surgical resection for thymic masses across 2 institutions were retrospectively analysed. Associations between serum tumour markers and TC diagnosis were assessed using the area under the receiver operating characteristic curve (AUC). The clinical utility of the identified tumour markers was further evaluated. RESULTS: In the discovery cohort from Shanghai Pulmonary Hospital (SPH), cytokeratin 19 fragment antigen 21-1 (CYFRA 21-1) levels were significantly higher in the TC group compared to both the thymoma group and the non-thymic epithelial tumour (non-TET) group (median of 2.38 ng/mL vs 1.39 ng/mL or 1.28 ng/mL, both P < .001), with AUC value of 0.778 (95% CI: 0.735-0.822) compared to thymoma and 0.808 (95% CI: 0.766-0.849) compared to non-TET group. Validation in the cohort from Renmin Hospital of Wuhan University further demonstrated significant discrimination of CYFRA 21-1 for TC diagnosis (vs thymoma: AUC = 0.681 [95% CI: 0.518-0.843]; vs non-TET: AUC = 0.801 [95% CI: 0.622-0.980]). Furthermore, high CYFRA 21-1 levels were also correlated with a shorter median disease-free survival compared to the low CYFRA 21-1 group (10.0 years vs 14.9 years, P < .001) in patients with TET in the SPH cohort. CONCLUSIONS: CYFRA 21-1 emerges as a reliable diagnostic biomarker for distinguishing TC from other thymic masses. Moreover, it holds promise for prognosis evaluation and potentially for recurrence surveillance.