Small cell lung cancer (SCLC) may be potentially curable. A correct diagnosis of cancer cell type is important and serum markers are of great value. Although several markers have been suggested, they have been of limited value because of insufficient specificity. To assess the value of serum neuron-specific enolase (S-NSE) as a possible marker of SCLC, the serum levels of 81 patients with SCLC (59 patients with extensive disease and 22 patients with limited disease) were compared with the serum levels of patients with non-small cell lung cancer (N-SCLC) and 93 patients with nonmalignant lung diseases. The S-NSE level also was measured in 104 patients with extensive disease of various other malignancies, including 71 solid tumors and 33 malignant hematologic disorders. From 105 healthy control subjects, the upper limit of the normal range (x + 2 standard deviations [SD]) was determined as 12.3 ng/ml. The S-NSE level was elevated in 78% of patients with SCLC, including 11 of 22 (50%) with limited disease and 52 of 59 (88%) with extensive disease. In contrast, the S-NSE level was raised only in 18% of patients with advanced N-SCLC (nine of 50) and 6% of patients with nonmalignant lung diseases (six of 93). Twelve patients (17%) with other solid malignant tumors and two patients (6%) with malignant hematologic disorders had raised S-NSE levels. Serial N-NSE levels were obtained in 13 patients with SCLC. S-NSE levels fell in all patients responding to chemotherapy and increased again with progression of disease. Our results indicate that S-NSE seems to be specific for SCLC (85%), whereas sensitivity seems to be dependent on the stage of disease. Further, S-NSE may be a useful marker for monitoring treatment and predicting relapse in patients with SCLC.

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