To study the behavior and possible correlations of
neuron-specific enolase (NSE) with other clinicobiological parameters, we measured the cytosolic levels of this marker by means of an immunoradiometric assay (IRMA) in 95 squamous cell lung
carcinoma samples. We also analyzed the levels of pS2,
tissue-type plasminogen activator (t-PA),
hyaluronic acid (HA), free beta subunit of
human chorionic gonadotropin (beta-HCG),
CYFRA 21.1 and CA 125 in cytosol. On the cell surface we analyzed the concentrations of
epidermal growth factor receptor (EGFR), HA, erbB-2
oncoprotein, CD44s, CD44v5 and CD44v6. Other parameters considered were clinical stage, lymph node involvement, histological grade (HG), ploidy and the cellular S-phase fraction measured by flow cytometry on nuclei obtained from fresh tissues. In the 95
squamous cell carcinomas the cytosolic levels of NSE varied from 4.5 to 2235 ng/mg
protein (median: 267) and were significantly higher (p < 0.001) than those observed in 38 samples of normal pulmonary tissue obtained from the same patients (range: 56-657; median: 141.5). When classifying
tumors according to the different parameters analyzed, we observed that the levels of NSE were higher in
aneuploid than in diploid cases (p = 0.046) and in those that were HG3 than in those that were HG2 (p < 0.001).
Tumors with high NSE levels (> 422 ng/mg
protein; 75th percentile) were more likely to have high S-phase values (p = 0.012) and were more frequently
aneuploid (p = 0.038) and HG3 (p < 0.001) than those with low levels of NSE (< 180 ng/mg
protein; 25th percentile). These results lead us to the following conclusions: 1) the cytosolic concentrations of NSE are significantly higher in
squamous cell carcinomas than in healthy pulmonary tissue, and 2) the cytosolic concentrations of NSE are not correlated with clinical stage or nodal involvement. However, in our study higher levels of the
enzyme were statistically correlated with
aneuploidy, histological grade 3 and S-phase. This may explain its association with poorer outcome and progression, but also the more favorable response of
tumors with elevated NSE to
chemotherapy, as suggested by other groups.