Carcinoembryonic antigen mRNA analysis detects micrometastatic cells in blood from lung cancer patients.

The current authors previously identified circulating cells expressing carcinoembryonic antigen (CEA) messenger ribonucleic acid (mRNA) in 80% of lung cancer patients bearing distant metastases. The current study prospectively validated the data on a novel cohort and extended the study to other mRNAs expressed by neoplastic cells. CEA, cytokeratin 19 and 20, aldolase A and epithelial glycoprotein 2 (EPG2) mRNA was analysed by reverse transcriptase-polymerase chain reaction in circulating cells from 19 healthy controls, and in biopsies and blood at diagnosis from 32 lung cancer patients monitored for 24 months. Aldolase A and cytokeratin 19 mRNA occurred in circulating cells of all controls; cytokeratin 20 was not expressed by any lung cancer biopsy. EPG2 mRNA occurred in all biopsies but not in the patients' circulating cells. CEA mRNA occurred in 29/32 (90.6%) biopsies and in 17/32 mRNA samples from circulating cells from lung cancer patients. Of these positive patients 12/17 developed metastases within 9 months of mRNA analysis. Three positive patients died, one was lost to follow-up, and one did not develop metastases within 24 months. Of the negative patients 12/15 did not develop metastases during the 24-month follow-up; one patient was lost to follow-up, one did not express CEA, and another developed metastases. Unlike in other neoplasias, cytokeratin 19 and 20, aldolase A and epithelial glycoprotein 2 messenger ribonucleic acid are not useful for the detection of circulating cancer cells in lung cancer. Carcinoembryonic antigen messenger ribonucleic acid analysis in circulating cells helps to identify lung cancer patients at a greater risk of metastases.

Demographic risk factors and lymphocyte populations in patients with tuberculosis and their healthy contacts.

SETTING: Campania, a southern region of Italy, and the Institute of Respiratory Diseases, Monaldi Hospital, University 'Federico II', Naples. OBJECTIVE: To evaluate clinical and socio-demographic risk factors for tuberculosis (TB) infection and/or disease. Peripheral blood lymphocytes from a sub-cohort of 19 patients and 53 contacts were studied by flow cytometry. DESIGN: A prospective study among patients with newly diagnosed pulmonary tuberculosis and their close contacts. RESULTS: A total of 90 patients and 277 contacts were enrolled. The prevalence of infection was 45% (95%CI 39-51%) among contacts. Age, sex, delay in diagnosis and treatment, cavitation on chest radiograph, cough, unwillingness to cover the mouth, and volume of air shared by close contacts and patients were investigated as potential risk factors for infection. Only delay in diagnosis of cases remained independently associated with an increased risk of infection (P < 0.0002), and hemoptysis was the only factor capable of reducing the delay significantly. The CD8+ CD28+ cytotoxic subset was significantly diminished in the patients (P < 0.001), whereas the CD8+ CD28- and CD8+ CD57+ (suppressor and NK-like subsets) were elevated (P < 0.001 and P = 0.04). CONCLUSIONS: These data show that delay in diagnosis of cases is a crucial factor for tuberculosis and that cytotoxic CD8+ cells play a primary role in immune response to tuberculosis.