[The expressions and diagnostic values of miR-18a and miR-21 in esophageal cancer].

Objective: To investigate the expressional levels and diagnostic values of miR-18a and miR-21 in esophageal carcinoma. Methods: The expressions of miR-18a and miR-21 in esophageal cancer tissues and adjacent tissues from 45 esophageal cancer patients, peripheral blood from 45 esophageal cancer patients and 50 healthy donors respectively were detected by RT-PCR. The expressions of miR-18a and miR-21 in normal esophageal epithelial cell HET-1A, esophageal cancer cell lines including ECA109, KYSE150 and TE1 were also detected. Chemiluminescence immunoassay was used to quantitatively detect the concentrations of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), CYRFA21-1 and TPA (tissue polypeptide antigen) in peripheral blood serum from esophageal cancer patients and healthy controls. Meanwhile, the diagnostic effects of miR-18a and miR-21 on esophageal cancer were compared with those of tumor markers in serum. Results: The expression levels of miR-18a and miR-21 in esophageal cancer cells ECA109, KYSE150 and TE1 were 1.64±0.17, 1.62±0.19, 1.46±0.12 and 20.52±1.48, 6.73±0.73, 1.43±0.19, respectively, higher than those in normal esophageal epithelial cells (both P<0.01). The expressions of miR-18a and miR-21 in esophageal cancer tissues were 32.48±28.62 and 8.67±11.98, respectively, significantly higher than those in adjacent tissues (all P<0.001). The expression levels of miR-18a and miR-21 in peripheral blood of patients with esophageal cancer were 12.66±11.92 and 9.15±8.14, respectively, significantly higher than those in the normal control group (both P<0.001). The receiver operating characteristic (ROC) curve analysis showed that the area under the curve of miR-18a and miR-21 for diagnosis of esophageal cancer were 0.948 and 0.913 5, respectively. Compared with traditional esophageal tumor markers, the expressions of miR-18a and miR-21 were more sensitive in the diagnosis of esophageal cancer. The sensitivity and accuracy of the expressions of miR-18a and miR-21 combined with traditional esophageal tumor markers in diagnosis of esophageal cancer can be further improved to 97.8% and 68.4%, respectively. Conclusion: Our study reveals that the expressions of miR-18a and miR-21 play important roles in the diagnosis of esophageal cancer and may be potentially novel biomarkers.

A sandwich-type immunosensor using Pd-Pt nanocrystals as labels for sensitive detection of human tissue polypeptide antigen.

A sandwich-type immunosensor was developed for the detection of human tissue polypeptide antigen (hTPA). In this work, a graphene sheet (GS) was synthesized to modify the surface of a glassy carbon electrode (GCE), and Pd-Pt bimetallic nanocrystals were used as secondary-antibody (Ab2) labels for the fabrication of the immunosensor. The amperometric response of the immunosensor for catalyzing hydrogen peroxide (H2O2) was recorded. And electrochemical impedance spectroscopy was used to characterize the fabrication process of the immunosensor. The anti-human tissue polypeptide antigen primary antibody (Ab1) was immobilized onto the GS modified GCE via cross-linking with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide (EDC/NHS). With Ab1 immobilized onto the GS modified GCE and Ab2 linked on Pd-Pt bimetallic nanocrystals, the immunosensor demonstrated a wide linear range (0.0050-15 ng ml(-1)), a low detection limit (1.2 pg ml(-1)), good reproducibility, good selectivity and acceptable stability. This design strategy may provide many potential applications in the detection of other cancer biomarkers.

Prognostic significance of TPA versus SCC-Ag, CEA and neopterin in carcinoma of the uterine cervix.

INTRODUCTION: Prognostic significance of squamous cell carcinoma antigen (SCC-Ag), tissue polypeptide antigen (TPA), carcinoembryonic antigen (CEA) and neopterin in cervical cancer patients was compared. MATERIALS AND METHODS: Pretreatment concentrations were determined in 138 women. RESULTS: Median age was 52 years, 85% squamous cell carcinomas, 15% adeno- or adenosquamous carcinomas were seen. In 36% Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage I, 24% stage II, 32% stage III and 8% stage IV was diagnosed. TPA was elevated in 22%, SCC in 68%, CEA in 42% and neopterin in 29%. These patients showed significantly worse overall survival in univariate analysis (p<0.001). TPA remained as independent prognostic factor in multivariate analysis. CONCLUSIONS: Elevation of TPA was associated with worse overall survival.

Tumor markers in pleural effusions.

AIM: The aim of this study was to determine the diagnostic capabilities of tumor markers in pleural effusion and their importance for assessment of the etiology of pleural effusions. PATIENTS AND METHODS: In pleural effusions from 166 patients hospitalized during the period 2003-2005 at the Department of Oncology and Radiotherapy, Faculty Hospital in Pilsen, the following tumor markers were determined: thymidine kinase (TK), neuron-specific enolase (NSE), cytokeratins [tissue polypeptide antigen (TPA), tissue polypeptide-specific antigen (TPS) and cytokeratin fragment 19 (CYFRA 21-1)], carcinoembryonic antigen (CEA) and mucinous markers (CA 15-3, CA 19-9, CA 125). The inflammatory marker procalcitonin-PCT was also assessed. RESULTS: Tumor markers CA 125, TPA, TPS were significantly elevated in exudates, irrespective of the etiology, as a non-specific reaction in mesothelial cells. TK had a sensitivity of over 80% for all the types of cancer examined, while CA 15-3 had a sensitivity of over 90%. CONCLUSION: Significant positivity of PCT and CA 15-3 in pleural effusions indicate a suspicion of inflammatory disease. Positivity of TK and CA 15-3 indicate a strong suspicion of malignant exudates.

Prognostic value of the serum tumour markers Cyfra 21-1 and tissue polypeptide antigen in malignant mesothelioma.

In malignant mesothelioma, survival is claimed to be related to age, duration of symptoms, performance status, histological subtype, stage and platelet count. However the exact prognostic value of these factors is still a matter of debate. We studied the two cytokeratin markers, Cyfra 21-1 and Tissue polypeptide antigen (TPA) for their significance in predicting survival retrospectively in 52 patients. Cyfra 21-1 and TPA were elevated in 26 (50%) and 30 (58%) patients, respectively, and were highly correlated (r = 0.98). Univariate analysis of data from 51 patients, showed a relation with survival for performance status (P = 0.010), thoracic pain (P = 0.014), platelet count (P = 0.027), Cyfra 21-1 (P = 0.002) and TPA (P = 0.003). Multivariate analysis identified independent prognostic significance for performance status, platelet count and Cyfra 21-1. In addition to performance status ( < 80 vs. > 80) the cytokeratin markers identified patients with good prognosis in a log rank test. Values of Cyfra 21-1 and TPA are significantly correlated.

Neuron-specific enolase is an effective tumour marker in non-small cell lung cancer (NSCLC).

BACKGROUND: Neuron-specific enolase (NSE) is a well known marker of small cell lung cancer. The present study was designed to assess the clinical value of NSE in non-small cell lung cancer (NSCLC), as compared to that of carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA). METHODS: The study comprised 448 new consecutive NSCLC patients seen from 1996 to 2001. A set of 30 anthropometric, clinical, physical, laboratory, radiological, and pathological variables was prospectively recorded for all patients. Patients were carefully followed-up, and their subsequent clinical course recorded. RESULTS: Increased values of NSE were present in 32% of the patients. Bivariate analyses showed that NSE, TPA and CEA were significantly correlated with each other, lactate dehydrogenase, tumour diameter, and disease extent. Univariate analyses showed that patients with elevated concentration of both NSE and TPA had significantly shorter survivals than patients with low values (30 [95% CI: 25-35] vs. 61 weeks [46-76], and 30 [CI: 24-36] vs. 59 weeks [40-79], respectively, P=0.0000). The Cox proportional hazards model including all the 22 variables significant in univariate analysis selected, in decreasing order of significance, the following variables: (1) N factor; (2) main treatment; (3) ECOG PS; (4) CNS metastasis; (5) age; (6) tumour cavitation; (7) NSE; (8) T factor; and (9) adrenal gland metastasis. CONCLUSIONS: This data indicates that serum assay of NSE is a useful marker also in NSCLC and a significant predictor of survival, independently of the other prognostic factors.

CYFRA 21-1, TPA-M, TPS, SCC-Ag and CEA in patients with squamous cell lung cancer and in chemical industry workers as a reference group.

In etiology of lung cancer chemical carcinogenesis seems to be a very important factor. In the studies presented here the diagnostic usefulness of tumor markers in lung cancer was evaluated, using as a reference group workers of a chemical plant producing chromite and chromate pigments. The investigations of CYFRA 21-1, TPA-M, TPS, CEA and SCC-Ag were performed before treatment in a group of 76 squamous cell lung cancer patients in different stages of disease and in a reference group of 75 workers of the chemical company, who had been exposed to hexavalent chromium for longer than 1 year and had no clinical or radiological symptoms of lung diseases. In the squamous cell lung cancer group concentrations of all analyzed tumor markers were considered to be significantly higher than in the reference group. TPA assay demonstrated higher diagnostic performance than CYFRA 21-1 and the remaining tumor markers. At 0.95 specificity, the sensitivity of TPA was 0.79, CYFRA 21-1 -0.76, of TPS -0.29 whilst of CEA and SCC-Ag -0.31. The univariate analysis showed a significant prognostic value for clinical stages, only for CYFRA 21-1 and SCC-Ag. A significant relationship between marker level and survival was observed for CYFRA 21-1 as well as SCC-Ag levels. In a multivariate analysis CYFRA 21-1 and/or TPS remained significant predictors of survival.

SPan-1 and exocrine pancreatic carcinoma. The clinical role of a new tumor marker.

AIMS OF THE STUDY: Considerable progress has been made in imaging techniques over the past few years, yet this has not resulted in the ability to reach an earlier diagnosis of exocrine pancreatic cancer. The search for a noninvasive diagnostic tool capable of early diagnosis has led to the development of a series of serum tumor markers. This article discusses the clinical evaluation of SPan-1 and its comparison with established markers such as CA 19.9, CEA, TPA and CA 242. METHODS: The markers were measured in preoperative serum samples collected from 46 patients who had undergone surgery for ductal carcinoma of the pancreas, 20 patients with chronic pancreatitis, and 23 patients with other digestive neoplasms. RESULTS: The sensitivity, specificity and diagnostic accuracy for pancreatic cancer were as follows: [table: see text] CONCLUSIONS: The antigenic determinant SPan-1, recognized by monoclonal antibodies, is elevated in sera of patients with exocrine pancreatic cancer. SPan-1 may be considered as an additional useful and reliable serum marker for the detection of this neoplasm, but it does not significantly improve the diagnostic accuracy obtained with CA 19.9.

Histopathological and prognostic evaluation of immunohistochemical findings in colorectal cancer.

Many immunohistochemical studies have investigated the relationship between immunohistochemical characteristics and histopathological findings in colorectal tumors. One of the most extensively studied markers has been tissue CEA, although the prognostic significance of this and other antigens is still uncertain. The authors report results relative to three tumoral antigens (carcinoembryonic antigen, CEA; tissue polypeptide antigen. TPA, and carbohydrate antigen 19-9, CA 19-9) determined by immunohistochemical methods in tissue samples of 52 colorectal carcinomas. The relationship between the immunohistochemical characteristics of the neoplasms and the clinicopathologic parameters, as well as their influence on the prognosis of the patients, were examined. Positive CEA reaction has a significant relationship with grade of differentiation of the tumor while diffuse cellular expression of this antigen often indicates neoplasms extending beyond the intestinal wall and invading the lymph vessels. The number of tissue antigens expressed is significantly related to the extent of tumor spread through the intestinal wall. A greater incidence of recurrence and shorter disease-free interval and survival were observed in neoplasms that expressed tissue TPA antigen or more than one tissue antigens. In the present study the latter parameter has demonstrated to have independent prognostic significance for the disease-free interval. Immunohistochemical evaluation of antigens in colorectal carcinoma tissue shows a possible independent prognostic value of the antigenic heterogeneity of tumors, which could be related to their different biological behavior.

Tumor markers and lung cancer: guidelines in a cost-limited medical organization.

The aim of our study was to evaluate the cost of the tumor marker assays most widely used in pneumological practice and the effectiveness of the percentage of DRG-based reimbursements absorbed by these assays. For this purpose we assessed the cost of lung tumor marker assays in Emilia Romagna compared to the DRG-based reimbursement of inpatients affected by lung diseases in whom the use of tumor markers is indicated. As an example, we evaluated the cost/effectiveness of the CEA assay in the differential diagnosis of 68 pleural effusions from 46 patients (20 benign diseases, 26 malignant). Because the CEA assay was not a substitute for cytology when this was not diagnostic, 41.3% of the resources were not efficiently spent. If the marker assay had been performed only in cases with negative cytology, we could have spared 14 of 46 tests. Moreover, since the expense lies predominantly in the cost of reagents (81.23%), we suggest as a routine procedure to collect and store samples for tumor marker assay in all cases; the test should be performed in a selected population of patients with negative cytology and "suspect" clinical outcome.

The concentrations of five tumor markers in both BAL fractions in lung cancer patients in relation to cigarette smoking.

BACKGROUND: Lung cancer is the leading cause of death from cancer. Tobacco is related to the development of this type of tumor due to genetic alterations and to the secretion of certain biological markers. Bronchogenic carcinomas secrete a series of biological substances known as tumor markers. Some of these markers, such as carcinoembryonic antigen, neuron-specific enolase, tissue polypeptide antigen (TPA), tissue polypeptide-specific antigen (TPS) and CYFRA 21.1, possess clear clinical value when analyzed in bronchoalveolar lavage (BAL) of patients with lung malignancies, particularly when they are analyzed in the two BAL fractions, bronchial (BF) and alveolar (AF), being more increased in the BF. For this reason, we intend to demonstrate that smokers with cancer secrete more biological substances in the BF and that the concentrations of these markers are higher in the BAL of smokers than in that of non-smokers. METHODS: The five aforementioned tumor markers were studied in the two BAL fractions of 52 lung cancer patients (46 smokers and 6 non-smokers). We performed BAL using 150 ml of 0.9% saline solution divided in three aliquots of 50 ml. The fluid obtained from the first 50 ml was the BF. The liquid from the other two aliquots was the AF. The five tumor marker concentrations were calculated in accord with the indications of the laboratory. RESULTS: The TPA and TPS levels in the BAL of lung cancer patients were more increased in the BF than in the AF, even when the patients were divided into smokers and non-smokers. When we compared smokers with non-smokers, the smokers had higher levels of TPS in the BF and of TPA in the AF. CONCLUSIONS: Thus, we believe that the cellular alterations produced by tobacco are responsible for the secretion of these tumor markers.

Significance of tissue polypeptide specific antigen (TPS) in diagnosis and monitoring of treatment in ovarian cancer.

Tissue polypeptide specific antigen (TPS) finds increasingly broad application in diagnosis and monitoring of treatment in ovarian cancer. Its sensitivity increases in parallel to clinical advancement of the tumor and to the grade of cellular differentiation. TPS may represent valuable supplementation of conventional markers in diagnosis of mucous carcinoma. Improved sensitivity and specificity of the technique for detection of ovarian cancer occur when two or more additional tumour markers are used in parallel. TPS has been found to represent a dependable index of surgical completeness. Determination of TPS in the sera of patients with ovarian cancer in the course of chemical treatment provides important information on the course of the neoplastic process and defines the response of the host to the applied treatment.

CA 15-3, ceruloplasmin and tissue polypeptide specific antigen as a tumour marker panel in breast cancer.

BACKGROUND: Tumour markers along with other tests, may be useful in the assessment of the prognosis, monitoring response to treatment and early detection of metastases in breast cancer. The most commonly used breast cancer antigen is CA 15-3. OBJECTIVE: To examine the value of CA 15-3, ceruloplasmin and tissue polypeptide specific antigen (TPS) panel in the monitoring of breast cancer. SUBJECTS: Serum concentrations of CA 15-3, ceruloplasmin and TPS were measured in 90 women: Fifteen controls, sixteen patients with benign breast disease (BBD), thirty one patients in remission and twenty eight patients with active breast cancer. RESULTS: The results of CA 15-3, ceruloplasmin and TPS estimates were separated into four groups. The patients not in remission were found to have significantly higher levels of CA 15-3 (p<0.0001) and ceruloplasmin (p<0.0001) compared with the other three groups. The difference between the patients in remission, BBD and the control group was not statistically significant (p>0.05) for CA 15-3 and ceruloplasmin. The difference for TPS between the patients in remission and the patients with active breast cancer was not statistically significant (p>0.05). The sensitivities of CA 15-3, ceruloplasmin, and TPS for detecting active breast cancer were 75.0%, 75.0%, and 78.0%, respectively. CONCLUSION: The highest sensitivity for active breast cancer detection was obtained by the combined use of three tumour markers. We concluded that there may be an advantage in using panels in the follow up of breast cancer patients, although so far such tests have too low a specificity to be of practical value in screening.

[Advances regarding tumor markers in bladder cancer]. / Avances en marcadores tumorales en cáncer vesical.

INTRODUCTION: Currently, there is not known tumoral marker for vesical carcinoma that would allow to distinguish when a surface tumour may become invasive. OBJECTIVE: To analyze the functionality of a series of biological substances (CEA, CA 50, CA 19.9 and TPS) in vesical carcinoma. MATERIAL AND METHODS: Between September 1992 and June 1994, a total of 385 biological specimens divided into two groups were analyzed. The first group comprised 271 serum samples from 81 control subjects and 190 patients with vesical carcinoma. The second group included 114 urothelial tissue samples (56 controls and 58 vesical carcinoma). Serum and tissue levels of CA, CA 50, CA 19.1 and TPS were determined in both groups by fluoroimmunoassay, RIA and IRMA, respectively. An statistical evaluation was done using Student's 't' and/or Mann-Whitney tests depending on whether data distribution adjusted to normal or not. RESULTS: Patients with vesical carcinoma, ana within this group those with infiltrant tumours, showed higher CEA serum levels. Also CEA tissue levels found in neoplastic vesical urothelium were higher than those in the control group (p < 0.05). Tissue levels were higher in infiltrant tumours. Higher TPS serum and tissue levels were found in the vesical tumours group. Same as with CEA, CA 50 also exhibited higher serum levels in the group with vesical Ca than in the controls (p < 0.01). Likewise, CA 50 tissue values were higher in the group with vesical Ca, more specifically in the infiltrant tumours group (p < 0.001). Statistically significant differences become apparent when the above values were compared to tissue samples from the control group (p < 0.001). On the other hand, serum CA 19.9 levels were lower in the vesical carcinoma group although tissue levels were higher in the vesical Ca group (p < 0.001). CONCLUSIONS: Transitional cell vesical carcinoma is a tumour that produces and secretes CEA, CA 50, CA 19.1 and TPS. CEA and CA 50 levels could be used as prognostic factors.

[Study of the cytosolic concentrations of the tissue poly-peptide specific (TPS) antigen in infiltrating ductal carcinomas of the breast. Positive relationship with hormone dependency and negative with cellular proliferation]. / Estudio de las concentraciones citosolicas del antígeno polipeptídico específico tisular (TPS) en carcinomas ductales infiltrantes de mama. Relación positiva con la hormonodependencia y negativa con la proliferación celular.

INTRODUCTION: The tissue-specific polypeptide antigen (TPS) is an epitope of the tissue polypeptide antigen (TPA) which is defined by the M3 monoclonal antibody and is related to cytokeratin 18. Several groups have demonstrated its value as a useful parameter in the follow-up of some tumors. This work has aimed to study the TPS cytosolic levels in infiltrating ductal carcinomas of the breast (IDC) and their possible correlations with other clinical-biological parameters. PATIENTS AND METHODS: The TPS was determined by means of an immunoradiometric assay (Beki Diagnostics. Sweden). Other parameters included in the study were the estrogen receptors (ER), progesterone receptors (PR), pS2, cathepsin D, tissue-type plasminogen activator (t-PA), tumor size, axillary lymph node involvement, distant metastases, histological grade, ploidy and S-phase. RESULTS: The TPS cytosolic levels ranged from 1.8 to 606.3 KU/mg prt. (median 110.2) and had a significant correlation with the ER (r: 0.721), PR (r: 0.287), cathepsin D (r: 0.550) and t-PA (r:0.436). The TPS positive (> 110.2 KU/mg prt.) carcinomas had higher levels of ER (p: 0.001), PR (p: 0.021), pS2 (p: 0.058), cathepsin D (p: 0.000) and t-PA (p: 0.053) than the TPS negative tumors. When the IDC were classified according to S-phase values, we observed that the positive cases (S-phase > 8.1%, which represents the median value of all carcinomas) had lower levels of TPS (p: 0.046) than the negative tumors. Likewise, the GoG1 cellular fraction correlated positively and significantly with the TPS cytosolic levels (p: 0.000). CONCLUSIONS: Based on our results, we suggest that there is a positive correlation between the TPS cytosolic levels and hormone-dependence parameters, as well as an inverse correlation between these and the cellular proliferation parameters. Based on the above, we consider that it is worthwhile to carry out further studies on cytosolic TPS in order to investigate its possible value as a prognostic parameter in breast carcinomas.

[Differences in assay sensitivity of selected tumor markers in head and neck neoplasms]. / Róznice czulosçi testów dla wybranych znaczników nowotworowych w raku plaskonablonkowym glowy i szyi.

Serum levels of seven tumor markers (AFP, Ca 19-9, CEA, TPA, NSE, ferritin and SCC-Ag) were measured in 95 patients with carcinoma of the head and neck to determine their sensitivity. The positive rates in 95 patients with the head and neck squamous cell carcinoma (SCC) were: 2.1% for AFP, 13.8% for Ca 19-9, 2.1% for CEA, 32.9% for TPA, 29.8% for ferritin, 53.2% for NSE and 46.8% for SCC-Ag in the first exam. Lowest sensitivity in the first exam of tests were in patients with SCC of the larynx: TPA-29.5%, ferritin-26%, NSE-51%, SCC-Ag 48%. Highest sensitivity of tests were in patients with SCC in other localisation than larynx: AFP-0%, Ca 19-9-23.5%, CEA-5.9%, TPA-38%, ferritin-35%, NSE-56%, SCC-62%. The sensitivity of the combination assay with these four tumor markers (TPA, ferritin, NSE, SCC-Ag) was higher than those obtained with individual markers. The sensitivity of the combination assay was for the group 95 patients 87.4% (first exam), for patients with SCC of the larynx 85.2% (first exam), for 34 patients with SCC in other localisations than larynx 91.2% (first exam). Combination assay with TPA, ferritin, NSE and SCC-Ag could be useful for screening and seems to be most useful for detection of recurrence in the follow-up.

Criteria to interpret cancer biomarker increments crossing the recommended cut-off compared in a simulation model focusing on false positive signals and tumour detection time.

BACKGROUND: Several criteria have been proposed to interpret increments in serological cancer biomarker concentrations starting from low baseline concentrations crossing the cut-off. None of the criteria have been compared for their ability to signal tumour growth when ≤2% false positive results are accepted. METHODS: The cancer biomarker Tissue Polypeptide Antigen was used as an example. Seven criteria to interpret increments in concentrations were investigated by computer simulations. Firstly, for each criterion, we identified a baseline concentration stratified for three levels of biological variation providing ≤2% false positive signals of tumour growth during one year of monitoring. Secondly, combining the steady state concentrations with rates of marker increase during tumour growth allowed calculation of the lengths of tumour detection times for each criterion. RESULTS: The number of false positive marker signals depended on the baseline concentration, the magnitude of biological variation, and the magnitude of the required increment defined in the criterion. The lengths of the tumour detection times also depended on the rates of marker increase. CONCLUSIONS: The results suggest that different types of criteria should be used within different intervals of below cut-off level concentrations if the rate of false positive signals of marker increments should be kept ≤2%.

An evaluation of tissue polypeptide antigen (TPA) in the two bronchoalveolar lavage fractions of lung cancer patients.

BACKGROUND: It has been proven that cytokeratins (CKs) are useful tumor markers for the follow-up, treatment monitoring and prognosis evaluation of lung cancer and among these, tissue polypeptide antigen (TPA) plays an important role. Nevertheless, only a small number of studies have been reported about their diagnostic capacity. Bronchoalveolar lavage (BAL) can be divided into two fractions: bronchiolar (BF) and alveolar (AF). For the above reasons, our aims were (1) to analyze the diagnostic usefulness of TPA in the BAL of lung cancer patients and (2) to observe if, in lung cancer patients, TPA levels in the two BAL fractions are different. This should mean that the study of tumor markers in the BAL should be carried out in both fractions to increase their diagnostic capacity. METHODS: We studied 289 BALs divided into two phases. In phase I, TPA was analyzed in the BAL of six groups of subjects (healthy persons, chronic bronchitis, asthma, respiratory infections, diffuse interstitial pulmonary diseases and lung cancer). In phase II, TPA was studied in both BAL fractions of a group of patients with lung cancer. RESULTS: We observed that TPA levels were significantly higher in the BAL of patients with bronchogenic neoplasias. In these patients, TPA was increased in the BF of the lavage in relation to the AF. In smoker patients with pulmonary carcinomas, TPA was higher in the AF of the BAL than in the lavage of non-smokers. This did not occur in the BF. We found no relation between the TPA concentrations and cancer histology. CONCLUSIONS: We believe that TPA is a useful tumor marker with diagnostic capacity and this capacity is increased when it is studied in the two BAL fractions. Smoking habit may play a role in the secretion of tumor markers by the tumor cells.