Differences in initial NSE levels in malignant and benign diseases of the thoracic wall.

BACKGROUND: Neuron-specific enolase (NSE) is widely used to follow-up patients with small cell lung cancer (SCLC). Since the NSE level can be influenced by a broad range of diseases and disorders a large study should be done to assess its level in various lung and non-lung tumors and benign diseases. METHODS: This research included 328 SCLC patients, 717 non-small cell lung cancer (NSCLC), 50 other thoracic cancers such as tumors of the mediastinum and mesothelioma, 35 non-pulmonary cancers like esophagus, breast and stomach cancer, 205 benign diseases, and 37 healthy individuals. The serum level of NSE was measured at initial diagnosis prior to therapy using electrochemiluminescence immunoassay (ECLIA, Roche Diagnostics). RESULTS: The high levels of NSE in SCLC differed significantly from all other groups. The results imply very good sensitivity of NSE in SCLC and good discriminatory power of NSE between SCLC and NSCLC. CONCLUSIONS: The NSE level in SCLC differs significantly from all other tested groups (p < 0.01). The highest values are seen in SCLC extensive disease. ROC curves revealed good discriminatory power of the initial NSE levels separating SCLC from other lung lesions. NSE can be used as a diagnostic tool for the early recognition of the neuroendocrine component of lung tumors and follow-up of SCLC patients.

ICTP in bone metastases of lung cancer.

Bone metastases often appear in advanced stages of lung cancer. They are the result of modulation of bone metabolism by tumor cells that migrated into bone microenvironment and degraded bone organic matrix. Measurement of C-terminal telopeptide of type I collagen (ICTP) in the serum of subjects with lung cancer with and without bone metastases and healthy population is the way to explore bone resorption. In 343 subjects included in this research ICTP level was significantly higher in the bone metastasis than other two groups. The existence of pathologic fracture significantly increased ICTP level. ICTP showed sensitivity of 66.0% in bone metastases at 95.0% specificity in lung cancer stages IA and IB. ICTP is a good diagnostic marker in detection of bone metastasis of lung cancer. Its level can distinguish lung cancer with and without bone involvement and can be used as an addition to standard techniques used in diagnostics of bone metastasis.

CYFRA 21-1 in non-small cell lung cancer--standardisation and application during diagnosis.

There is no ideal tumour marker at present. The clinical application of CYFRA 21-1 is possible once a thorough standardisation process is carried out. Standardisation is achieved by determining the reference range in asymptomatic population, benign and malignant lung diseases, and benign and malignant diseases of other organs. Furthermore, it depends on knowledge of research population characteristics, patient medical histories and individual diagnostic procedure results, the size of research target samples and the clinically defined control groups. The cut-off level of CYFRA 21-1 for non-small cell lung cancer (NSCLC) is 1.72 ng/mL in the Croatian population. It is based on the clinically applicable sensitivity of 78% and specificity of 95% in benign lung diseases. The cut-off value is verified by clinical findings. For clinicians the level of CYFRA 21-1 is an early sign of NSCLC in relation to all the benign lung diseases and all the benign diseases of other organs, of which it was confirmed that they can influence the above level, provided that NSCLC is verified using standard diagnostic methods. The level of CYFRA 21-1 is also influenced by the time of sampling in relation to other diagnostic invasive procedures. The marker is clinically applicable if clinical findings verify it; otherwise, it is useless. This research has involved 343 healthy persons, 474 patients with a benign disease and 4440 patients with a malignant disease, 2453 of whom suffer from NSCLC. The sensitivity of CYFRA 21-1 in NSCLC is 78%, in squamous cell lung cancer (SQC) 84.6%, in adenocarcinomas (AD) 74.3% and in large cell lung cancer (LCC) 75.3%. The level of CYFRA 21-1 differs significantly between healthy persons, benign and malignant diseases (p<10(-3)). There are differences between the three histological types of NSCLC (p<10(-6)) and according to T and N (p<10(-3)). The level of CYFRA 21-1 prompts clinicians to repeat the clinical procedure during diagnosis, and helps to detect the disease earlier and implement treatment in NSCLC. We have achieved high concordance between marker findings and clinical diagnostic.

Determining the cut-off value of pro-gastrin releasing peptide (ProGRP) in lung cancer according to population characteristics.

The standardisation process consisted of determining tumour marker levels in all relevant population groups which are connected with the biology of the marker in normal and tumourous cells. This makes clinical application possible. ProGRP serum levels were measured in 273 healthy subjects, 176 patients with benign diseases and tumours, 200 with small cell lung cancer (SCLC), 294 with non-small cell lung cancer (NSCLC), 21 with carcinoid tumour, 93 with undifferentiated lung cancer, 35 with mixed SCLC-NSCLC, and 189 with other malignancies. ProGRP levels in patients with SCLC and SCLC-NSCLC were significantly higher than in all the other groups (p = 5.4 x 10(-3)). Moreover, in SCLC patients ProGRP levels significantly correlate with the extent of the disease and the patients' smoking habit. The cut-off level of ProGRP for SCLC is 65.89 pg/mL in the Croatian population. It is based on 96.8% specificity in benign diseases which cause problems in differential diagnosis. The sensitivity of ProGRP was 85% at the time of SCLC diagnosis.