Combined serum carcinoembryonic antigen and cytokeratin 19 fragment levels provide a sensitive biomarker for lymph node metastasis in extramammary Paget's disease.

Abstract

Most cases of extramammary Paget's disease are diagnosed at an early stage. For advanced cases, few effective treatments are available and the prognosis is poor. Therefore, developing sensitive biomarkers for metastatic cases is a critical challenge. Carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA) are two potentially useful biomarkers. In the present retrospective large-scale study, we identified other potential biomarkers of lymph node metastasis. Patients with extramammary Paget's disease who visited our dermatology clinic between April 2004 and March 2019 (n=138; mean age, 73.4years; 85 men and 53 women) were enrolled in the study. The patients were divided into three groups according to the presence of regional lymph node metastasis and distant metastasis to evaluate the relationship between metastasis and various tumor markers: serum CEA, carbohydrate antigen (CA)19-9, CA125, CA15-3 and CYFRA. For distal metastasis, each biomarker had high sensitivity and specificity. The sensitivities and specificities for regional lymph node metastasis were as follows: CEA, 50.0% and 88.6%; CA19-9, 50% and 89.5%; CA125, 0% and 98.2%; CA15-3, 0% and 96.0%; and CYFRA, 66.7% and 95.0%, respectively. We also analyzed biomarker combinations. The sensitivity and specificity of the combination of all five biomarkers (CEA, CA19-9, CA125, CA15-3 and CYFRA) were 83.3% and 70.9%, respectively. The sensitivity of the combination of just CEA and CYFRA was also 83.3%. Screening for combinations of these biomarkers will facilitate the detection of early lymph node metastasis in patients with extramammary Paget's disease.