Tumour markers in serum, bronchoalveolar lavage and biopsy cytosol in lung carcinoma: what environment lends the optimum diagnostic yield?

BACKGROUND: The aim of this study was to assess the diagnostic yield of the tumour markers carbohydrate antigen (CA 125), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), squamous cell carcinoma antigen (SCC) and specific tissue polypeptide antigen (TPS) in serum, bronchoalveolar lavage (BAL) and biopsy cytosol in a group of patients with bronchogenic carcinoma. METHODS: Serum, BAL and biopsy cytosol samples were collected in a group of 85 patients with benign or malignant pulmonary diseases. After appropriate processing, tumour markers were determined by enzyme immunoassay. The diagnostic yields (sensitivity, specificity and accuracy) in each environment (serum, BAL or biopsy) were obtained by using "ROC" curves. RESULTS: Determined individually, CA 125, NSE and SCC show the greatest diagnostic accuracy in cytosol. CEA and TPS do so in BAL. CEA is the most relevant marker in serum and BAL, and CA 125 in cytosol. When the different tumour markers are associated, they offer better overall yields for all except TPS. CONCLUSIONS: For the factors evaluated in this study, determination of CEA in BAL was clinically the most useful marker in comparison with serum and cytosol determinations, although the latter may also be helpful in certain situations. Although there is no specific tumour marker for lung cancer, the combination of several can be used to monitor most patients with lung cancer.

DNA aneuploidy, S-phase fraction and nuclear p53 positivity in non-small cell lung carcinoma.

OBJECTIVES: Surgical resection currently offers the best option for managing non-small cell lung carcinoma (NSCLC) but its efficiency is limited by subsequent tumor recurrence. We evaluated whether flow cytometric study and the p53 gene staining pattern may be useful in this respect. DESIGN AND METHODS: We took biopsy samples of 40 patients with operable NSCLC to study the frequency of aneuploidy, proliferative activity, and alterations in the p53 tumor suppressor gene and compared them with clinicopathological parameters such as age, gender, smoking, histological type, tumor size, and degree of differentiation. To study DNA content, the nuclei were analyzed by flow cytometry using a FACS flow cytometer (Becton-Dickinson) equipped with an argon ion laser, with a propidium iodide excitation of 488 nm. We used the immunohistochemical technique for p53 analysis in samples of paraffin-embedded tissue corresponding to the same patients from whom fresh tissue was taken. RESULTS: Nuclear p53 staining was detected in 66.7% of the samples; 69.4% of the cases revealed aneuploid DNA histograms and 59% presented with an S phase fraction of more than 12%. Comparison with clinicopathological parameters showed that p53 protein was associated significantly with histological classification (p = 0.04), gender (p = 0.01), and smoking (p = 0.04). CONCLUSIONS: Immunodetection of p53 overexpression and DNA ploidy in the bronchial epithelium may be a useful tool in any future multifactorial analysis in such tumors for identifying previous lesions that may progress to malignancy.

Tumor markers in lung cancer: does the method of obtaining the cut-off point and reference population influence diagnostic yield?

OBJECTIVES: The aim of this study was to evaluate the clinical usefulness of the tumor markers CA125, CEA, NSE, SCC, and TPS in a group of patients with lung cancer. We estimated the influence of the method for choosing the cut-off point and of considering as a reference population either healthy controls or patients with some form of non-neoplastic pulmonary disease (NNPD). DESIGN AND METHODS: The tumor markers were determined using enzyme immunoassay techniques, and their diagnostic yield was evaluated using ROC curves and their correlation with the percentages between false and true positives. The diagnostic parameters of the tumor markers are presented in 116 patients with lung cancer and compared with a group of 25 healthy controls and another group of 80 patients with some form of NNPD. We determined on the one hand the cut-off points resulting from the best sensitivity-specificity balance in the ROC curves and on the other those resulting from considering a specificity of 95%. With the two cut-offs we studied the different diagnostic parameters: sensitivity, specificity and accuracy or area below the ROC curve. RESULTS: Optimum diagnostic yield is obtained when we choose the cut-off point determined by the best balance of sensitivity and specificity in the ROC curves and take a healthy population as a reference group. The cut-off values for CA125, CEA, NSE, SCC, and TPS were 24 U/mL, 2.8 ng/mL, 9.8 ng/mL, 1.6 ng/mL, and 67.8 U/L, respectively. CONCLUSIONS: Our results suggest that in future studies on tumor markers, a group of healthy subjects should be used as a reference population and ROC curves should be used to obtain the optimum cut-offs.