No abstract

ABSTRACr Among lung cancers small cell carcinoma is the most sensitive to chemotherapy and radiation. This has emphasised the importance of an accurate diagnosis of this cell type, and the present study examined the use of serum neurone specific enolase (NSE) as a diagnostic marker for small cell carcinoma. NSE was measured in pretreatment sera from 103 patients with small cell carcinoma and in sera from relevant controls, including patients with other lung cancers, non-malignant lung diseases, and healthy adults. Serum NSE concentration was raised (> 25 ng/ml) in 72% of patients with small cell carcinoma. Ninety one per cent of patients with extensive disease and 50% of patients with limited disease were serum NSE positive. Patients with extensive disease in general had higher serum NSE concentrations than patients with limited disease. No definite difference in serum NSE positivity could be shown between oat cell and intermediate cell subtypes. Out of 51 patients with other lung cancers, four (8%) had a raised serum concentration, whereas all patients with non-malignant diseases and healthy individuals had normal serum NSE concentrations. Serum NSE determination seems to be a valuable tool for the diagnosis of small cell carcinoma.Small cell carcinoma of the lung, accounting for about 20% of lung cancers,' has proved to be the lung cancer most sensitive to combination chemotherapy and radiation. This has resulted in a considerable improvement of survival time and, in a small group of patients with small cell carcinoma, a complete cure has even been documented.2 A correct diagnosis of cancer cell type is therefore important and a serum marker would be of great value for identifying cases of small cell carcinoma. Several serum markers have been suggested but found to be of limited value, mainly because of insufficient specificity.3 Some promising reports on neurone specific enolase as a serum marker for small cell carcinoma have, however, been published recently.4 5

Amplified and increased expression of the myc family of protooncogenes (c- and N-myc) has been described to be associated with rapid proliferation in a number of cell lines, including small cell lung cancer (SCLC). In SCLC, c-myc was demonstrated to be amplified in a subset of SCLC cell lines denoted as variant type, which show a more aggressive way of growth in vitro. The N-myc oncogene, which has extensive homology in the second exon with c-myc, has been shown to be implicated in the oncogenesis of several primary tumors, including SCLC. The authors describe, using in situ hybridization, that increased expression of the N-myc oncogenes in primary biopsies from 15 untreated patients with SCLC are strongly associated with poor response to chemotherapy, rapid tumor growth, and short survival.

The respective pretreatment prognostic impacts of the following markers were evaluated in 125 patients with small cell lung cancer (SCLC): lactic dehydrogenase (LDH), serum thymidine kinase (S-TK), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and tissue polypeptide antigen (TPA). More traditional clinical and serologic markers were also evaluated. Univariate analysis showed that all of the biochemical markers mentioned above, the Karnofsky index (KI) and the patient's sex were related to both the stage of disease (limited/extensive disease: LD/ED) and to survival. The strongest marker for the clinical stage was S-TK, whereas TPA showed the strongest relationship with survival. Multivariate analyses produced a model consisting of S-TK, CEA, NSE, and the patient's sex for determining the clinical stage. To compare the prognostic capacity of easily determined biochemical and simple clinical variables to the more resource-demanding variable of the clinical stage, three multivariate analyses in relation to survival were performed: (1) biochemical markers and simple clinical variables; (2) LD/ED and simple clinical variables; and (3) all available variables. The model obtained from the first analysis included TPA, KI, age, and the patient's sex; the model from the second analyses included LD/ED, patient's age, and KI; and the model from the third analysis, TPA, KI, age, sex, and LD/ED. Indices based on these three multivariate models were calculated for each patient and the prognostic capacity of these indices was compared. Pretreatment serum marker levels also had the capacity to predict both the grade and the duration of the response to therapy.

No abstract