Frequency and clinical implications of monoclonal antibody detection of tumor-associated antigens in serum of patients with lung cancer. We previously showed that a panel of monoclonal antibodies (MAb) (5E8, 5C7, and 1F10) that detect serum tumor-associated antigens (TAA) could distinguish patients with lung cancer from those without to a highly significant degree. However, among patients with lung cancer, the frequency and clinical importance of serum TAA expression were not established. Therefore, we analyzed the serum and initial clinical characteristics of 52 Philadelphia VA patients with newly diagnosed lung cancer seen over a 13-month period. A modified semiquantitative ELISA was employed to determine MAb reactivity. Our cohort was characterized by a mean age of 65 +/- 9 year (SD) and mean Karnovsky score of 74 +/- 10; marked weight loss was present in 28 subjects, and 39 presented with either Stage III or IV disease. The panel detected TAAs in 38 of 52 cases (sensitivity 73%; 95% Cl, 60-83%), including 13 of 22 squamous cell, 9 of 12 adenocarcinoma, 10 of 11 undifferentiated, and 6 of 7 small cell carcinomas. No significant differences were found between the reactive and nonreactive patients in terms of age, stage at presentation, histologic subtype, performance status, or weight loss. However, 1F10 and 5C7 were each associated with a greater risk of early death by Cox proportional hazard analysis (p = 0.017 and 0.006, respectively) even when other prognostic variables are accounted for. We conclude that specific serum TAA can be detected in the majority of lung cancer patients with all major histologic subtypes in a cohort with advanced tumors and poor prognostic indices. 