• carcinoembryonic antigen;
  • CYFRA 21-1;
  • HER2/neu;
  • paraneoplastic;
  • pleural fluid


Cytology fails to detect neoplastic cells in approximately 40% to 50% of malignant pleural effusions (PEs), which commonly accompany lung adenocarcinomas. The diagnostic accuracy of various tumor markers in lung adenocarcinoma-associated cytologically negative pleural effusions (LAC-CNPEs) has been poor. The current study attempted to maximize diagnostic efforts in distinguishing LAC-CNPEs from benign PEs.


PE samples were collected from 74 patients with lung adenocarcinoma with associated cytologically positive (41 patients) and negative (33 patients) PEs, and from 99 patients with benign conditions including tuberculosis (26 patients), pneumonia (28 patients), congestive heart failure (25 patients), and cirrhosis (20 patients). The authors evaluated the diagnostic sensitivity and optimal cutoff points for the tumor markers HER2/neu, CYFRA 21-1, and carcinoembryonic antigen (CEA) to distinguish LAC-CNPEs from benign PEs.


Mean levels of HER2/neu, CYRFA 21-1, and CEA were found to be significantly higher in LAC-CNPEs compared with benign PEs (P = .0050, P = .0039, and P < .0001, respectively). The cutoff points for HER2/neu, CYFRA 21-1, and CEA were optimally set at 3.6 ng/mL, 60 ng/mL, and 6.0 ng/mL, respectively. Their sensitivities ranged from 12.1%, to 30.3%, to 63.6%, respectively. CEA combined with CYFRA 21-1 increased diagnostic sensitivity to 66.7%. The false-positive rates of these markers in benign PEs were 6.1%, 2.0%, and 0%, respectively.


The combination of CEA with CYFRA 21-1 appears to provide the best differentiation between LAC-CNPEs and benign PEs to date using 2 tumor markers, and allows for the early diagnosis and early treatment of approximately two-thirds of affected patients. Cancer (Cancer Cytopathol) 2013;121:483–8. © 2013 American Cancer Society.