The significance of NSE and CEA as a differentiation marker for the cellular heterogeneity of small cell lung cancer.

Neuron-specific enolase (NSE) and carcinoembryonic antigen (CEA) levels in the culture supernatant of the 65 pulmonary carcinoma cell lines: Small cell lung cancer (SCLC) 18, large cell carcinoma 14, squamous cell carcinoma 14, adenocarcinoma 14 and adenosquamous cell carcinoma 5, were measured by a radioimmunoassay (RIA). The mean value of NSE was 30.8+/-22.4 ng/ml and 9.2+/-8.7 ng/ml in SCLC and non-SCLC, respectively. The mean value of CEA was 15.1+/-20.9 ng/ml and 26.6+/-72.3 ng/ml in SCLC and non-SCLC, respectively. A significant difference in NSE levels was obtained between SCLC cell lines and non-SCLC cell lines. In SCLC cell lines, a significant inverse proportional correlation was observed between NSE and CEA levels. The CEA production tended to be higher in cells with low levels of NSE than in those with high NSE production. With respect to correlation between marker production and growth characteristics of SCLC cells in vitro, significantly higher NSE and lower CEA levels were found in cells growing with floating colony or neurite like characteristics (classic cell type) than those in cells with epithelial or intermediate growth characteristics (variant cell type). A significant positive correlation between NSE levels and the survival periods was found in follow-up studies of 10 patients who underwent surgery with complete resection of the primary tumor. All of 4 long term survivors over 3 years after surgery had significantly high NSE and relatively low CEA producing tumors. The relationship of these markers to clinical status of the patient suggests that an analysis for correlation of NSE and CEA levels in SCLC patients may be useful to discriminate between a pure neuroendocrine SCLC tumor and a mixed small cell/large cell tumor, and in monitoring therapeutic effect and prognosis of each patient.