bromochloroacetic-acid and Lung-Diseases

This diagnostic seminar discusses the current status of the principles and problems of cytology as it is applied to the diagnosis of lung cancer. This discussion is divided into four major parts. Part I presents a discussion of cytopreparatory techniques and cytology of the lung in the absence of cancer. The cytology of benign proliferations which may mimic cancer is emphasized. The role of cytology in the diagnosis of pulmonary infectious organisms is noted. Part II discusses lung cancer as manifested in specimens of sputum, bronchial washings, and bronchial brushings. Part III presents some data on the validity of cytology with respect to role of specimen number and type in lung cancer diagnosis and cell typing in lung cancer. The continued usefulness and importance of multiple specimens of sputum for lung cancer diagnosis are documented. Part IV presents a brief synopsis of fine needle aspiration biopsy of lung cancer.

Topics: Adenocarcinoma; Aspergillus; Biopsy, Needle; Blastomyces; Bronchi; Carcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Nucleus; Coccidioides; Cryptococcus neoformans; Cytodiagnosis; Cytological Techniques; Cytoplasm; Epithelium; Histoplasma; Humans; Keratins; Lung Diseases; Lung Diseases, Fungal; Lung Diseases, Parasitic; Lung Neoplasms; Macrophages; Metaplasia; Pneumocystis; Sputum; Strongyloides; Suction; Virus Diseases

Mallory's body filament assembly includes polypeptides of the cytokeratin class of intermediate filaments and also higher molecular weight polypeptides normally found only in the cytokeratins of mature keratinocytes of the epidermis. These additional polypeptides may alter both the morphologic characteristics and increase the resistance to dissolution of the filaments by Ca++-activated protease activity. Thus, it is likely that the kinetics of Mallory's body filament assembly and dissolution favor growth of the filaments. In rodents fed certain carcinogens, Mallory's body formation has been accompanied by the induction of the oncofetoenzyme gamma-glutamyl transpeptidase (GGT), suggesting that Mallory's body formation, like GGT induction, is a phenotypic change related to the process of neoplastic transformation in rodents.

Topics: Animals; Carcinogens; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Cytoskeleton; gamma-Glutamyltransferase; Griseofulvin; Humans; Intermediate Filament Proteins; Keratins; Liver; Liver Diseases; Liver Neoplasms; Liver Neoplasms, Experimental; Lung; Lung Diseases; Phosphorylation; Protein Precursors

Airway epithelial basal cells are known to be critical for regenerating injured epithelium and maintaining tissue homeostasis. Recent evidence suggests that the alpha7 nicotinic acetylcholine receptor (nAChR), which is highly permeable to Ca(2+), is involved in lung morphogenesis. Here, we have investigated the potential role of the alpha7 nAChR in the regulation of airway epithelial basal cell proliferation and the differentiation of the human airway epithelium. In vivo during fetal development and in vitro during the regeneration of the human airway epithelium, alpha7 nAChR expression coincides with epithelium differentiation. Inactivating alpha7 nAChR function in vitro increases cell proliferation during the initial steps of the epithelium regeneration, leading to epithelial alterations such as basal cell hyperplasia and squamous metaplasia, remodeling observed in many bronchopulmonary diseases. The regeneration of the airway epithelium after injury in alpha7(-/-) mice is delayed and characterized by a transient hyperplasia of basal cells. Moreover, 1-year-old alpha7(-/-) mice more frequently present basal cells hyperplasia. Modulating nAChR function or expression shows that only alpha7 nAChR, as opposed to heteropentameric alpha(x)beta(y) nAChRs, controls the proliferation of human airway epithelial basal cells. These findings suggest that alpha7 nAChR is a key regulator of the plasticity of the human airway epithelium by controlling basal cell proliferation and differentiation pathway and is involved in airway remodeling during bronchopulmonary diseases.

Topics: alpha7 Nicotinic Acetylcholine Receptor; Animals; Binding Sites; Bungarotoxins; Cell Differentiation; Cell Proliferation; Cells, Cultured; Cystic Fibrosis Transmembrane Conductance Regulator; Epithelial Cells; Humans; Keratins; Lung Diseases; Membrane Proteins; Mice; Mice, Knockout; Phenotype; Phosphoproteins; Receptors, Nicotinic; Regeneration; Respiratory Mucosa; Zonula Occludens-1 Protein

Clara cell 10 kDa protein (CC10) is the major secretory protein of Clara cells and is thought to play a protective role in the lung owing to its anti-inflammatory properties. There is little information on the anatomical distribution of CC10-positive cells in rat lung following lipopolysaccharide (LPS) challenge. We have determined the expression of CC10 along the tracheobronchial tree in saline-treated and LPS-treated rats. Saline-treated rats showed sporadic CC10 staining in central airways and abundant staining in bronchioles. In transitional airways, most cells were positive except for squamous cells. Following LPS challenge, there was a reduction in staining in the upper airways but little change within bronchioles. Squamous epithelia within the transitional airways now showed positive staining. These cells also co-stained for pancytokeratin and appeared to co-localize with surfactant D- and Ki67-positive cells, indicating the presence of a dedifferentiated cell type with both epithelial and pneumocyte phenotypes. These data show that diffuse inflammatory injury results in generalized loss of CC10 in central airways. Conversely, the transitional airways showed evidence of a dedifferentiated population of squamous cells that now stained for CC10. We hypothesize that this is an attempt by peripheral lung to maintain alveolar sac integrity during an inflammatory episode.

Topics: Acute Disease; Administration, Inhalation; Animals; Biomarkers; Bronchi; Enzyme Inhibitors; Keratins; Ki-67 Antigen; Lipopolysaccharides; Lung Diseases; Male; Pulmonary Surfactant-Associated Protein D; Rats; Respiratory Mucosa; Uteroglobin

Exhaled breath condensate (EBC) is increasingly studied as a noninvasive research method of sampling the lungs, measuring several biomarkers. The exact site of origin of substances measured in EBC is unknown, as is the clinical applicability of the technique. Special techniques might be needed to measure EBC biomarkers.. To assess biomarker concentrations in clinical disease and investigate the site of origin of EBC, we compared EBC and bronchoalveolar lavage (BAL) biomarkers in 49 patients undergoing bronchoscopy for clinical indications.. We measured exhaled nitric oxide, 8-isoprostane, hydrogen peroxide, total nitrogen oxides, pH, total protein, and phospholipid (n = 33) and keratin (n = 15) to assess alveolar and mucinous compartments, respectively. EBC was collected over 10 min using a refrigerated condenser according to European Respiratory Society/American Thoracic Society recommendations, and BAL performed immediately thereafter.. 8-Isoprostane, nitrogen oxides, and pH were significantly higher in EBC than in BAL (3.845 vs. 0.027 ng/ml, 28.4 vs. 3.8 microM, and 7.35 vs. 6.4, respectively; p < 0.001). Hydrogen peroxide showed no difference between EBC and BAL (17.5 vs. 20.6 microM, p = not significant), whereas protein was significantly higher in BAL (33.8 vs. 183.2 microg/ml, p < 0.001). Total phospholipid was also higher in EBC, but keratin showed no difference. No significant correlation was found between EBC and BAL for any of the biomarkers evaluated either before or after correction for dilution.. In clinical disease, markers of inflammation and oxidative stress are easily measurable in EBC using standard laboratory techniques and EBC is readily obtained. However, EBC and BAL markers do not correlate.

Topics: Biomarkers; Breath Tests; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Dinoprost; Exhalation; Female; Humans; Hydrogen Peroxide; Inflammation; Keratins; Lung Diseases; Male; Middle Aged; Nitric Oxide; Phospholipids

Using current diagnostic criteria, this work summarizes the microscopic review of 16 proliferative squamous lesions, previously diagnosed as cystic keratinizing squamous cell carcinoma, in the lungs of rats from a 2-year inhalation study with pigment-grade titanium dioxide particles.. In the aftermath of two international pathology workshops designed, in part, to establish histological criteria for classifying pulmonary keratin lesions, these lesions were evaluated by four pathologists using current diagnostic criteria.. Unanimous agreement was reached as to the diagnosis of each of the lesions. Two of the lesions were diagnosed as squamous metaplasia and one as a poorly keratinizing squamous cell carcinoma. The remaining 13 lesions were diagnosed as non-neoplastic pulmonary keratin cysts.. These keratin cysts are a species-specific lesion that is unique to the rat lung under conditions of particle overload exposure.

Topics: Animals; Cysts; Dose-Response Relationship, Drug; Dust; Environmental Exposure; Female; Inhalation Exposure; Keratins; Lung Diseases; Lung Neoplasms; Male; Neoplasms, Squamous Cell; Pulmonary Alveoli; Rats; Species Specificity; Titanium

To determine whether chorioamnionitis has an impact on the extent of apoptosis and proliferation in fetal lungs. Fetuses exposed to chorioamnionitis have an increased risk of aquiring lung tissue damage in utero.. Lung tissue sections from 35 stillborn fetuses were used in this study. Chorioamnionitis-exposed fetuses were subdivided depending on whether pneumonia was diagnosed (n = 13) or not (n = 10); 12 unaffected fetuses served as controls. Apoptotic and proliferating cells were determined by in-situ terminal deoxytransferase-mediated dUTP nick end labelling (TUNEL) assay and by anti-Ki67 immunohistochemistry, and quantified. The median apoptotic index in lungs of chorioamnionitis-exposed fetuses increased 2.4-fold compared with chorioamnionitis-negative stillborn controls (P = 0.043) and rose 21.6-fold when chorioamnionitis-exposed fetuses additionally developed pneumonia (P < 0.001). Compared with the proliferation index of the control group (PI = 2.3), the median percentage of proliferating cells in the lungs of chorioamnionitis-exposed fetuses decreased (PI = 1.4) (P = 0.036), but increased 1.8-fold (P = 0.036) in fetal lungs of the chorioamnionitis/pneumonia group. By double labellings combining the TUNEL assay or the Ki67 antigen with cell marker proteins, we identified distal airway epithelial cells as the cell type undergoing apoptosis in chorioamnionitis-exposed fetal lungs, while epithelial, endothelial and smooth muscle cells proliferated. Immunolabellings of cleaved caspases -8 and -9 revealed that apoptosis is mediated via initiator caspase-8.. Chorioamnionitis induces apoptosis of distal airway epithelial cells via the caspase-8 pathway and interferes with the normal proliferative activity of epithelial, endothelial, and smooth muscle cells in fetal lungs. Thus, apoptosis and proliferation are an important feature of chorioamnionitis-associated lung injury in utero.

Topics: Antigens, CD34; Apoptosis; Autopsy; Caspase 3; Caspase 8; Caspases; Cell Proliferation; Chorioamnionitis; Female; Fetus; Gestational Age; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Keratins; Ki-67 Antigen; Lung; Lung Diseases; Male; Pregnancy

From 40 pigs rejected for human consumption at slaughter due to an apparent presence of pyemic lung lesions (defined as disseminated processes containing pus and/or necrotic material), the lungs, spleen, liver, and kidneys were subjected to an extended macroscopic examination. Several lung lesions were sampled from each animal for histological and bacteriological examination. Samples from the kidneys and spleens were also subjected to bacteriological examination. At gross level, four groups of lung lesions were identified: 1) disseminated foci with contents of pus and/or necrotic material (n=26); 2) disseminated or multifocally located ecchymoses with a central area of fibroplasia (n=9); 3) non-pneumonic lesions, i.e., disseminated areas of atelectasis (n=1) or haemorrhagic areas developing due to the process of slaughter (n=1); and 4) suppurative lesions without a disseminated distribution pattern (n=3). Histologically, the disseminated suppurative/necrotic foci were identified as: A) abscesses (n=10); B) necrotic lesions (n=6); and C) ectatic or ectatic-like bronchioles with contents of pus and necrotic material (n=10). The macroscopic observation of disseminated centres of fibroplasia with peripheral ecchymoses (n=9) was confirmed histopathologically. The livers of five pigs contained multiple areas of chronic interstitial fibrosis related to migration of Ascaris suum larvae ("milk spotted liver"). Such hepatic lesions were significantly (p<0.01) related to the simultaneous occurrence of disseminated pulmonary ecchymoses with a central area of fibroplasia. Generally, all lung lesions of each individual animal contained identical monocultures of bacteria following this pattern: Staphylococcus aureus (abscesses); Actinomyces hyovaginalis (necroses); S. aureus, A. hyovaginalis, and Arcanobacterium pyogenes (ectatic and ectatic-like bronchioles). Areas with fibrosis were sterile or contained bacteria considered to be a result of contamination. Apart from one kidney, from which S. aureus was cultured, all other organs were sterile. It is concluded that difficulties exist in differentiating pulmonary pyemic lesions from non-pyemic lesions at the gross level. Thus, it was not possible to distinguish between abscesses/necroses and ectatic bronchioles, the pathogenesis of the latter being uncertain. However, the chronic non-pyemic lesions related to the migration of A. suum larvae should be identified by the absence of pus/necrosis. S. aureus was predominantly

Topics: Abscess; Actinomyces; Actinomycosis; Animals; Keratins; Lung; Lung Diseases; Necrosis; Pneumonia, Bacterial; Suppuration; Sus scrofa; Swine Diseases

The aim of our study was to assess the clinical value of CYFRA 21-1 tumor marker and carcinoembryonic antigen (CEA) as diagnostic tools that are complementary to cytology in the diagnosis of malignant mesotheliomas.. We measured CEA and CYFRA 21-1 in the pleural effusions (PEs) and serum of 106 patients (benign lung disease, 34 patients; bronchogenic and metastatic carcinoma, 40 patients; mesothelioma, 32 patients).. CEA and CYFRA 21--1 levels were determined by means of two commercial enzyme immunoassays.. The cutoff levels of CYFRA 21--1 and CEA in malignant PEs, selected on the basis of the best diagnostic efficacy, were 41.9 ng/mL and 5.0 ng/mL, respectively. In all neoplastic PEs, CYFRA 21--1 and CEA sensitivity was 78% and 30.6%, respectively, with a specificity of 80% and 91%, respectively. The sensitivity of CYFRA 21--1 and CEA in patients with mesothelioma was 87.5% and 3.1%, respectively. The results of the CYFRA 21--1 assay were positive in 17 of 19 cases of mesothelioma (89.5%) with a negative or uncertain cytology. The association of the tumor marker assay and the cytology allowed a correct diagnosis in 30 of 32 cases of mesothelioma (93.7%).. This study suggests that CYFRA 21--1 would provide a useful parameter for the differential diagnosis between benign and malignant PE from mesothelioma when the result of cytology is negative or uncertain and the clinical context does not allow a more aggressive approach. Moreover, the association of CYFRA 21--1 with CEA could provide details for a differential diagnosis between mesotheliomas and carcinomas. In fact, an elevated CYFRA 21--1 level with a low CEA level is highly suggestive of mesothelioma, whereas high levels of CEA alone or high levels of both the markers suggest a diagnosis of malignant PE, excluding mesothelioma.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma; Diagnosis, Differential; Humans; Keratin-19; Keratins; Lung Diseases; Lung Neoplasms; Mesothelioma; Pleural Effusion, Malignant; Pleural Neoplasms; Sensitivity and Specificity

Our purpose was to determine whether peripheral blood biomarkers MUC1 and CK19 could be used to complement imaging studies in differentiating benign from malignant indeterminate pulmonary nodules or masses detected on computed tomography CT. One hundred and eighteen patients had a thoracic CT and blood drawn for tumor marker reverse transcriptase-polymerase chain reaction analysis. Thirty-five of the 118 patients had an indeterminate pulmonary nodular opacity on CT, and the findings then were correlated with the reverse transcriptase-polymerase chain reaction results. The sensitivity and specificity for the markers in determining malignancy was calculated. Thirteen of the 35 opacities on CT proved to be benign, and 22 proved to be lung cancer. Among the patients with indeterminate pulmonary abnormalities, polymorphic epithelial mucin protein 1 had a sensitivity and specificity for lung cancer of 100% and 46%, respectively. Cytokeratin 19 had a sensitivity and specificity for lung cancer of 95% and 8%, respectively. These preliminary data showed that serum biomarkers polymorphic epithelial mucin protein 1 and cytokeratin 19 were not specific for lung cancer, although patients with an indeterminate pulmonary abnormality and negative markers were unlikely to have lung cancer. Integration of imaging studies with the appropriate biomarkers may prove useful in evaluating indeterminate pulmonary nodules or masses.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Diagnosis, Differential; Female; Humans; Keratins; Lung Diseases; Lung Neoplasms; Male; Middle Aged; Mucin-1; Peptide Fragments; Pilot Projects; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tomography, X-Ray Computed

Serum pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) is a metabolite of type I collagen comprising 90% or more of organic substances in bone. Its usefulness as a marker of bone metastasis from malignant tumors is expected.. We measured ICTP to evaluate its clinical usefulness for diagnosis of bone metastasis in 140 patients with lung cancer. For comparison, serum carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA 21-1), gastrin-releasing peptide precursor (ProGRP), alkaline phosphatase and calcium were simultaneously measured. ICTP was measured by double-antibody radioimmunoassay.. ICTP was significantly higher in patients with bone metastasis from lung cancer than in the group without bone metastasis, patients with other pulmonary diseases or healthy control subjects and showed excellent sensitivity and specificity, indicating that this marker is highly useful for complementary diagnosis of bone metastasis from lung cancer. Moreover, the survival duration was significantly shorter in the ICTP-positive group than in the ICTP-negative group, suggesting that ICTP can be a prognostic factor in lung cancer.. It is suggested that measurement of ICTP is worthwhile as a serological diagnostic method of bone metastasis from lung cancer. Moreover, since repeated measurements are possible, this measure was considered very helpful in complementary diagnosis of bone metastasis and also as a standard to determine the timing of examinations such as bone scintigraphy.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Antigens, Neoplasm; Biomarkers; Biomarkers, Tumor; Bone Neoplasms; Calcium; Carcinoembryonic Antigen; Carcinoma, Large Cell; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Collagen; Collagen Type I; Female; Gastrointestinal Hormones; Humans; Keratin-19; Keratins; Lung; Lung Diseases; Lung Neoplasms; Male; Middle Aged; Peptide Fragments; Peptides; Prognosis; Recombinant Proteins; Sensitivity and Specificity; Survival Rate

CYFRA 21-1 and ProGRP have recently been established as new tumor markers for lung cancer. However, there are few reports evaluating concentrations in their bronchoalveolar lavage (BAL) fluid. In this study, we examined 81 patients with benign lung disease. The mean values of CYFRA 21-1 in the BAL fluid of each lung disease were as follows: bronchiolitis obliterans organizing pneumonia (BOOP), 3.9 +/- 2.1 ng/ml (positive rate 50%); collagen vascular disease associated interstitial pneumonia (CVD-IP), 10.7 +/- 15.7 ng/ml (positive rate 50%); diffuse panbronchiolitis (DPB), 4.2 +/- 6.4 ng/ml (positive rate 29%); idiopathic pulmonary fibrosis (IPF), 1.5 +/- 2.1 ng/ml (positive rate 17%); pulmonary infiltration with eosinophilia, 6.3 +/- 7.1 ng/ml (positive rate 44%); sarcoidosis, 4.6 +/- 6.2 ng/ml (positive rate 27%); and healthy volunteer (HV), 0.6 +/- 0.6 ng/ml; and total, 4.4 +/- 5.6 ng/ml (positive rate 32%). The mean values of ProGRP in the BAL fluid were as follows: DPB, 5.0 +/- 7.6 pg/ml (positive rate 0%); IPF, 6.4 +/- 10.6 pg/ml (positive rate 0%); HV, 12.4 +/- 8.3 pg/ml; and total, 5.6 +/- 8.7 pg/ml (positive rate 0%). These results indicate that the two tumor markers have no disease specificity in benign lung disease.

Topics: Antigens, Neoplasm; Bronchoalveolar Lavage Fluid; Cryptogenic Organizing Pneumonia; Humans; Keratin-19; Keratins; Lung Diseases; Lung Diseases, Interstitial; Peptide Fragments; Peptides; Pulmonary Eosinophilia; Recombinant Proteins

Cell lysis and tumor necrosis release cytokeratin, a tumor marker of lung cancer, into the serum. The serum cytokeratin level can also be elevated in benign cavitary lung diseases. The purpose of this study was to evaluate whether Cyfra 21-1 can differentiate malignant lung diseases from benign diseases with cavitary lesions.. This study is a retrospective review of the case records of patients with lung lesions seen during a 4-year period from January 1993 to May 1996.. Serum Cyfra 21-1 levels were measured in 306 patients with lung cancer (n = 143) or benign lung disease (n = 163). The patients were grouped according to radiologic evidence of cavitary lung lesions. Lung cancer included both non-small cell (n = 123) and small cell (n = 20) lung cancers, and the benign diseases include tuberculosis (n = 87), abscess (n = 26), pneumonia (n = 4), and others (n = 46).. Although Cyfra 21-1 clearly differentiated cavitary lung cancer (15.0, 9.1-29.8 ng/ml, median and interquartile range, n = 39) from benign cavitary disease (P < 0.001), and noncavitary lung cancer from benign noncavitary disease (1.7, 0.9-2.6 ng/ml, n = 108, P < 0.001), it could not differentiate noncavitary lung cancer (5.0, 2.1-12.4 ng/ml, n = 104) from benign cavitary diseases (3.3, 1.4-8.3 ng/ml, n = 55, P = 0.45).. Serum Cyfra 21-1 is a useful tumor marker for differentiating benign from malignant lung diseases. However, different cutoff values are needed, depending on the presence of cavitary lesions. We recommend cutoff values of 30 ng/ml for cavitary lung diseases and 6 ng/ml for noncavitary lung diseases. If there are no radiologic data, a cutoff value of 15 ng/ml is recommended.

Topics: Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Diagnosis, Differential; Female; Humans; Keratin-19; Keratins; Lung Diseases; Lung Neoplasms; Male; Middle Aged; Reference Values; Retrospective Studies; Sensitivity and Specificity

The aim of this prospective study was to assess the diagnostic value of the imaging modalities (chest radiography, spiral computed tomography (SCT) and high-resolution computed tomography (HRCT)) and the tumour markers (carcinoembryonic antigen (CEA), cytokeratin marker (CYFRA 21-1) and neuron-specific enolase (NSE)) in the differentiation of malignant (MSPLs) from benign solitary pulmonary lesions (BSPLs).. Solitary pulmonary lesions (SPLs) were examined, evaluated and then completely removed by surgery in 104 consecutive patients (MSPLs n = 81, BSPLs n = 23). Chest radiography was performed with frontal and lateral views, SCT was carried out with a slice thickness of 8 mm and HRCT with a slice thickness of 1 mm and a 12-cm field of view. For the tumour marker analysis, serum concentrations were determined 1-3 days prior to surgery by ELISA for CEA and CYFRA 21-1 and by IRMA for NSE using commercially available assay kits. The cut-off values were set at 3 ng/ml (for non-smokers) and 5 ng/ml (for smokers) for CEA, at 3.3 ng/ml for CYFRA 21-1 and at 12.5 ng/ml for NSE.. Using any one of the characteristics with a significance level of P <0.01, the identification of MSPLs using chest radiography showed a sensitivity of 64.2% and a specificity of 82.6%, using SCT a sensitivity of 88.9% and a specificity of 60.9% and using HRCT a sensitivity of 91.4% and a specificity of 56.5%. For the identification of MSPLs using CEA a sensitivity of 27.2% and a specificity of 87.0% (accuracy of 40.4%) was observed. Using CYFRA 21-1 a sensitivity of 19.8% and a specificity of 100.0% (accuracy of 37.5%) and using NSE a sensitivity of 13.6% and a specificity of 100. 0% (accuracy of 32.7%) was found.. Using chest radiography, SCT and HRCT, a precise morphological assessment of the periphery of the pulmonary lesion and the adjacent visceral pleura is necessary to distinguish MSPLs from BSPLs. Tumour markers used alone or in combination with the imaging methods brought no additional benefits, in terms of sensitivity and accuracy, over the diagnostic imaging methods alone. However, the tumour markers exhibited a far superior specificity (100% for CYFRA 21-1 and NSE) compared with the imaging methods.

Topics: Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Diagnosis, Differential; Female; Humans; Keratin-19; Keratins; Lung; Lung Diseases; Lung Neoplasms; Male; Middle Aged; Phosphopyruvate Hydratase; Predictive Value of Tests; Prospective Studies; Sensitivity and Specificity; Tomography, X-Ray Computed

We examined the incidence and association of bronchiolization of the alveoli with non-small cell lung cancer in lung resection specimens from 2 patient groups: those with non-small cell lung cancer and those diagnosed with a variety of non-neoplastic lung conditions. We observed marked variation in bronchiolization of the alveoli morphology ranging from normal to severely atypical and developed a classification scheme based on growth pattern, cell number and cytologic criteria. Patterns of differentiation, proliferation and growth factor receptor and oncogene expression were studied using immuno-histochemical and in situ hybridization techniques. While low-grade (0-I) bronchiolization of the alveoli lesions demonstrated markers similar to normal bronchiolar epithelium, a significant decrease in the Clara cell 10 kDa protein and tubulin and an increase in surfactant protein-A expression were observed in high-grade (II-III) lesions. Focal p53 expression was detected in 2 high-grade lesions, while c-myc mRNA and cJun protein were observed in all grades. No correlation was observed between bronchiolization of the alveoli incidence and histologic tumor type. A comparison of marker expression in lesions and tumors from the same case revealed a negative correlation between cytokeratin-14 and c-erbB-2 immuno-reactivity. Only one bronchialization of the alveoli lesion was found in the non-neoplastic patient group. We conclude that up to 12% of non-small cell lung cancer resection specimens contain bronchiolization of the alveoli lesions which exhibit altered morphology and patterns of differentiation.

Topics: Bronchi; Carcinoma, Non-Small-Cell Lung; Cell Differentiation; Humans; Immunoenzyme Techniques; Keratins; Lung Diseases; Lung Neoplasms; Proliferating Cell Nuclear Antigen; Proteins; Proteolipids; Proto-Oncogene Proteins; Pulmonary Alveoli; Pulmonary Surfactant-Associated Proteins; Pulmonary Surfactants; Receptors, Growth Factor; Uteroglobin

The aim of this study was to evaluate the diagnostic value of a new tumour marker, cytokeratin fragment 19 (CYFRA 21-1), in bronchoalveolar lavage fluid (BALF) for the diagnosis of lung cancer. The cross-sectional study included 36 patients with lung cancer, 19 with benign lung diseases and 13 control subjects. In the group with cancer, BAL was performed in the cancer-involved lung and in the opposite lung. Results in BALF were expressed both as absolute concentrations (ng ml-1) and referred to total protein (TP) (ng mg-1 TP), and results in plasma were expressed in ng ml-1. In BALF, there was no significant different between cancer and control groups. Using the 95th percentile of levels obtained in benign lung disease in BALF (specificity 95%) as the cut-off point, the sensitivity of CYFRA 21-1 was 13%. Positive and negative predictive values (PPV and NPV) at different pretest probabilities, and positive and negative gains were obtained applying a Bayesian analysis. Results showed low positive gains for PPV (maximal increase of 22%) and almost none for NPV (negative gains < 5%). In plasma, CYFRA 21-1 provided a sensitivity of 65%. The combination of BALF and plasma tumour marker levels showed a sensitivity of 69%. Therefore, measurement of CYFRA 21-1 in BALF has poor diagnostic value in lung cancer.

Topics: Antigens, Neoplasm; Bayes Theorem; Biomarkers, Tumor; Bronchoalveolar Lavage Fluid; Cross-Sectional Studies; Female; Humans; Keratin-19; Keratins; Lung Diseases; Lung Neoplasms; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Sensitivity and Specificity

The aim of this study was to evaluate the diagnostic value of three tumour markers, squamous cell carcinoma (SCC) antigen, carcinoembryonic antigen (CEA) and CYFRA 21.1, in lung cancer using a Bayesian analysis to obtain the predictive values for different pretest probabilities or prevalences. A cross-sectional study included 94 patients with lung cancer, 40 with benign lung disease, and 40 healthy controls. SCC antigen and CEA were measured in blood samples by microparticle enzyme immunoassay (MEIA), and CYFRA by enzyme-linked immunosorbent assay (ELISA). The results of tumour marker determinations were expressed as percentiles, and showed significantly higher levels in the cancer group than in the two control groups. Taking the 95th percentile of benign lung diseases as the cut-off point (specificity 95%), the following sensitivities were found: SCC 41%, CEA 31% and CYFRA 79%. After a Bayesian analysis, the best results for the three tumour markers were found in prevalences of 30-40%. The highest incremental gain was obtained by CYFRA (at prevalence of 36%, positive and negative predictive value approximately 90%). The three tumour markers were included in a stepwise regression analysis to predict lung cancer, and CYFRA was the only selected variable. We conclude that CYFRA 21.1 may be a useful marker in lung cancer when there is an intermediate pretest probability of disease.

Topics: Adenocarcinoma; Aged; Antigens, Neoplasm; Bayes Theorem; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoenzyme Techniques; Keratin-19; Keratins; Logistic Models; Lung Diseases; Lung Neoplasms; Male; Middle Aged; Predictive Value of Tests; ROC Curve; Sensitivity and Specificity; Serpins

To elevate the diagnostic value of the serum cytokeratin 19 fragment (CYFRA 21-1) and compare it with carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA) in bronchogenic carcinoma, the sera of 161 patients (58 with benign pulmonary disease and 103 with bronchogenic carcinoma) was investigated using immunoradiometric assay. Sensitivities for CYFRA 21-1, CEA and TPA (using 3.5 ng ml-1, 5.0 ng ml-1, 110 U l-1, respectively, cut-off values corresponding to a 95% specificity for benign pulmonary disease) in bronchogenic carcinoma were 64, 47 and 61%, respectively. Positive CYFRA 21-1 levels were identified in 75% of patients with squamous cell carcinoma (n = 36), in 67% with adenocarcinoma (n = 45), in 17% with large cell carcinoma (n = 6), and in 50% with small cell lung cancer (SCLC) (n = 16). However, CYFRA 21-1 levels were not significantly different between squamous cell carcinoma and the other histological types. The sensitivity of the combined measurement of CYFRA 21-1 with any other tumour marker was significantly higher than that of CYFRA 21-1 measurement alone. Elevated CYFRA 21-1 levels were observed in 44% of Stages I and II (n = 18) and 72% of Stage III and IV (n = 69) patients with non-small cell lung cancer (P < 0.05). A significant inter-marker correlation was observed between CYFRA 21-1 and TPA (n = 103, r = 0.448, P < 0.0001). Twenty-one patients were monitored by CYFRA 21-1, and significantly different changes in progressive patients (P = 0.0058) and regressive patients (P = 0.016) were obtained. These results indicate that CYFRA 21-1 may be not only a sensitive tumour marker in the diagnosis of bronchogenic carcinoma, but also a useful marker for the monitoring of bronchogenic carcinoma.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Bronchogenic; Carcinoma, Large Cell; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Humans; Immunoradiometric Assay; Keratin-19; Keratins; Lung Diseases; Lung Neoplasms; Male; Middle Aged; Sensitivity and Specificity; Tissue Polypeptide Antigen

In this study we looked at what useful information cytokeratin fragment detected by antibodies BM 19-21 and KS 19-1 (CYFRA 21.1), carcinoembryonic antigen (CEA), neurone-specific enolase (NSE), tissue polypeptide specific antigen (TPS), and tissue polypeptide antigen (TPA) gave when measured prospectively. All patients who were suspected of having lung cancer and who underwent diagnostic bronchoscopy in this hospital between July 1994 and May 1995 were included in the study. Of 184 patients, 87 were subsequently found to have intrathoracic malignancy, 93 were found to have benign lung disease and four were lost to follow-up. CYFRA 21.1 was the most efficient marker in differentiating benign from malignant disease, with a sensitivity of 54% and a positive predictive value of 96%. Thirty seven patients who had a negative bronchoscopy subsequently turned out to have malignant disease. Either CYFRA 21.1 or CEA was elevated in 26 (70%) of such patients. Multivariate analysis showed that only CYFRA 21.1 and CEA contributed significantly to the discriminatory power of the data. We conclude that measurement of cytokeratin fragment detected by antibodies BM 19-21 and KS 19-1 and carcinoembryonic antigen at the time of bronchoscopy significantly increased the diagnostic yield in this population and was especially useful in those patients in whom tumour biopsy was not possible at bronchoscopy.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Diagnosis, Differential; Humans; Keratin-19; Keratins; Lung Diseases; Lung Neoplasms; Peptides; Phosphopyruvate Hydratase; Predictive Value of Tests; Sensitivity and Specificity; Tissue Polypeptide Antigen

Topics: Biomarkers; Carcinoma, Non-Small-Cell Lung; Humans; Keratins; Lung Diseases; Lung Neoplasms

The CYFRA 21-1, a newly developed sandwich enzyme-linked immunosorbent assay (ELISA), was used to measure soluble cytokeratin 19 fragment in serum that is expressed in simple epithelium and its malignant counterpart. The present study was designed to investigate whether CYFRA 21-1 is a sensitive and specific tumor marker for non-small cell lung cancer.. CYFRA 21-1 assay, using two specific monoclonal antibodies (KS 19.1 and BM 19.21) for cytokeratin 19, was measured in 312 serum samples, including 164 lung cancer, 118 benign pulmonary disease, and 30 healthy individuals. The sensitivity of CYFRA 21-1 was also compared with two other markers, carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC), in 164 patients with lung cancer.. The median value of healthy individuals was 1.3 ng/mL (95th percentile 1.8). In patients with benign pulmonary diseases, the median was 1.5 ng/mL (95th percentile 2.9). There is no significant difference between sexes, smoking habit, and the subgroups of benign pulmonary disease, such as tuberculosis, pneumonia, or COPD. Using the cutoff value of 3.3 ng/mL, defined at 95% specificity for benign lung disease, the sensitivities of CYFRA 21-1 for squamous cell carcinoma (n=74), adenocarcinoma (n=54), undifferentiated large cell carcinoma (n=11), and small cell lung cancer (n=25) were 62%, 39%, 36%, and 20%, respectively. Despite the cell types, the sensitivities of CYFRA 21-1 in non-small cell lung cancer (NSCLC, n=169) were 51% (CEA 42%, SCC 20%). The sensitivity of CEA was significantly higher in patients with adenocarcinoma (58%) than other markers; while in patients with squamous cell carcinoma, CYFRA 21-1 assay has the highest sensitivity. The median level of CYFRA 21-1 in squamous cell carcinoma is significantly higher than that of other cell types (Mann-Whitney test, p<0.001). The serum level and sensitivity of CYFRA 21-1 were well correlated with staging and tumor size in squamous cell carcinoma. The CYFRA 21-1 values were measured for monitoring progression of disease in 20 patients with squamous cell carcinoma. There is significant difference in paired observation of CYFRA 21-1 level in patients with progressive disease (Wilcoxon signed-rank test, p<0.05), but no difference was observed in patients with stabilized disease (p>0.1).. For patients with NSCLC, especially in squamous cell carcinoma, CYFRA 21-1 is not only a sensitive and specific tumor marker, but also may be a useful adjunctive marker for disease monitoring.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Disease Progression; Enzyme-Linked Immunosorbent Assay; Epithelium; Female; Humans; Keratins; Lung Diseases; Lung Diseases, Obstructive; Lung Neoplasms; Male; Neoplasm Staging; Pneumonia; Sensitivity and Specificity; Serine Proteinase Inhibitors; Serpins; Sex Factors; Smoking; Tuberculosis, Pulmonary

The sensitivity and specificity of Cyfra 21-1 as marker for lung cancer was evaluated in comparison with carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and neuron-specific enolase (NSE). Patients with histologically verified lung cancer and different groups without lung cancer were investigated. Sensitivity of Cyfra 21-1 (cut-off level 2.9 micrograms/l) was 40% for non-small cell lung cancer (NSCLC), 60% for rare histological types and 21% for small cell lung cancer (SCLC). In NSCLC sensitivity of Cyfra 21-1 was 35% for squamous cell carcinoma and 41% for adenomous carcinoma. The highest sensitivity for CEA was 45% in NSCLC, with 57% in the subtype of adenomous cell carcinoma; for SCC 30% was achieved in squamous cell carcinoma and for NSE 66% sensitivity was reached in SCLC. In our patients Cyfra 21-1 and CEA appeared equally useful for evaluating patients with NSCLC.

Topics: Adult; Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Diagnosis, Differential; Humans; Immunoradiometric Assay; Keratins; Lung Diseases; Lung Neoplasms; Middle Aged; Neoplasm Staging; Phosphopyruvate Hydratase; Sensitivity and Specificity; Serpins

We examined two recently described cytokeratin markers, CYFRA 21-1 (cytokeratin fragment recognized by KS 19-1 and BM 19-21 antibodies) and TPS (specific M3 epitope of the tissue polypeptide antigen), in 405 lung cancer patients (91 small-cell and 314 non-small-cell lung cancers) and 59 patients presenting with nonmalignant pulmonary disease. Sensitivity-specificity relationship, as analyzed by receiver operating characteristic curves, demonstrated a higher accuracy of CYFRA 21-1 in comparison with TPS in both small-cell and non-small-cell lung cancers. Thresholds of 3.6 ng/ml and 140 U/L for CYFRA 21-1 and TPS respectively gave a 90% to 95% specificity. Sensitivity of CYFRA 21-1 was the highest in squamous-cell carcinomas (0.61) and the lowest in small-cell lung cancers (0.36), whereas sensitivity of TPS did not vary significantly according to histology (overall sensitivity, 0.40). In non-small-cell lung cancers, both serum CYFRA 21-1 and serum TPS distributions varied significantly according to Mountain's stage of the disease, nodal status, tumor status, and performance status, inasmuch as the worse each above-mentioned variable became, the higher the median and interquartile serum marker level was. Neither CYFRA 21-1 nor TPS was able to accurately discriminate between stage IIIa (marginally resectable) and stage IIIb (unresectable) non-small-cell lung cancers, however. In both small-cell and non-small-cell lung cancers, univariate survival analyses demonstrated that either a CYFRA 21-1 level over 3.6 ng/ml or a TPS level over 140 U/L significantly indicated a poor survival rate. In the whole population, taking into account other significant variables, Cox's model analysis demonstrated that a poor performance index, an advanced stage of the disease, the presence of metastases, elevated serum lactate dehydrogenase, and high serum CYFRA 21-1 (odds ratio, 1.74; 95% confidence interval, [1.33-2.27] were independent prognostic variables. We concluded that CYFRA 21-1 is a significant determinant of survival. Other applications of cytokeratin markers in lung cancer are still limited.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Female; Humans; Keratins; Lung Diseases; Lung Neoplasms; Male; Middle Aged; Peptides; Prognosis; Prospective Studies; Sensitivity and Specificity; Tissue Polypeptide Antigen

We report two cases of small pleural nodules showing the distinctive histologic appearance of adenomatoid tumor. Both lesions were discovered incidentally during surgery in patients undergoing lung resection for unrelated intrapulmonary masses: lung carcinoma in one case and histoplasmosis in the other. The tumors were composed of a focal proliferation of epithelioid cells forming vacuoles and tubular spaces in a fibrous stroma, as seen in adenomatoid tumors from other sites. The differential diagnosis in both cases included metastatic signet ring cell carcinoma. The mesothelial nature of the lesions was supported by immunohistochemical and ultrastructural evidence. The tumor cells in both cases were positive for cytokeratin but negative for carcinoembryonic antigen and LeuM1. One case was also negative for BER-EP4, B72.3, CD34, and Factor VIII. Electron microscopy in this case demonstrated well-developed basal laminae, desmosomes, and numerous slender microvilli along the luminal surfaces of the tumor cells. Adenomatoid tumors are regarded as a benign variant of mesothelioma. Despite the abundance of mesothelial cells in the pleura, adenomatoid tumors are apparently extremely rare in this location. Separation from malignant lesions such as adenocarcinoma and epithelioid hemangioendothelioma is important.

Topics: Adenomatoid Tumor; Aged; Basement Membrane; Breast Neoplasms; Carcinoma, Ductal, Breast; Cell Nucleus; Cytoplasm; Desmosomes; Female; Granuloma; Humans; Immunohistochemistry; Keratins; Lung Diseases; Microscopy, Electron; Microvilli; Middle Aged; Neoplasms, Second Primary; Pleural Neoplasms

To evaluate the usefulness of CYFRA 21-1 and SCC Ag in the diagnosis of squamous cell carcinoma (SQC) of the lung, we tested sera from 124 patients with lung cancers (squamous cell ca 72, adenoca 22, large cell ca 4, small cell ca 18 and undetermined 8) and 78 patients with inflammatory lung diseases (bronchitis 24, bronchiectasis 29, tuberculosis 19 and others 6) using immunoradiometric assay kit for cytokeratin fragment 19 (CYFRA 21-1) and radioimmunoassay kit for SCC Ag. The serum CYFRA 21-1 and SCC Ag were significantly higher in lung cancer patients compared with control subjects. However, the significant difference was restricted only to SQC. In patients with SQC, CYFRA 21-1 and SCC Ag showed significantly higher levels according to the advanced anatomic stages (stage I-IIIa vs. stage IIIb, IV, p < 0.05). There was a good correlation between CYFRA 21-1 and SCC Ag (r = 0.41, p < 0.001). Receiver operating characteristic (ROC) curves were generated from results of both tumor markers and areas under the curves (AUC) were calculated. AUC of CYFRA 21-1 (0.93) were significantly larger than that of SCC Ag (0.77) for the diagnosis of SQC (p < 0.05). Therefore, we conclude that CYFRA 21-1 is superior to SCC Ag in the diagnosis of squamous cell carcinoma of the lung.

Topics: Aged; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Humans; Keratins; Lung Diseases; Lung Neoplasms; Male; Middle Aged; Sensitivity and Specificity

Cyfra 21-1 is a novel marker for non small cell lung cancer. Up to now only few data about the value of Cyfra 21-1 in the diagnosis of malignant and non-malignant pulmonary diseases are available. Further the effect of long-time cigarette consumption on serum concentrations of Cyfra 21-1 has not been described. Aim of this study therefore was the determination of Cyfra 21-1 in different malignant and non-malignant pulmonary diseases and in healthy smokers and nonsmokers.. Sera of healthy individuals (control group, n = 121; 63 smokers and 58 nonsmokers), patients with chronic bronchitis (n = 50), lung fibrosis (n = 38), exogen allergic alveolitis (n = 32), lung tuberculosis (n = 45), sarcoidosis (n = 30), small cell lung cancer (n = 60), squamous cell carcinoma (n = 53), non-small cell carcinoma (n = 29) and adenocarcinoma (n = 52) were analyzed.. Within the control group no significant differences of the Cyfra 21-1 serum concentration were observed between smokers and nonsmokers. Serum concentrations of Cyfra 21-1 were similar in the control group, patients with non-malignant pulmonary diseases and patients with small cell lung cancer whereas serum concentrations were significantly increased in patients with non-small cell lung cancer, adenocarcinoma and squamous cell carcinoma.. The data confirm the high sensitivity and specific of Cyfra 21-1 for the differential diagnosis between malignant and non-malignant pulmonary diseases as well as small cell and non-small cell lung cancer.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Diagnosis, Differential; Female; Humans; Keratins; Lung Diseases; Lung Neoplasms; Male; Middle Aged; Predictive Value of Tests; Reference Values; Smoking

Despite extensive research, the role of the commonly employed tumour markers in the diagnosis of lung carcinoma is yet to be clarified. The utility of a new marker, CYFRA 21-1, in the preoperative evaluation of patients with bronchogenic carcinoma was investigated. CYFRA 21-1 was determined with a radiometric assay in serum of 280 patients with lung cancer and 208 patients with various nonmalignant lung diseases. The levels of the marker were significantly higher in lung cancer patients. Among benign lung diseases, elevated CYFRA 21-1 levels were found in pulmonary fibrosis. Using a cut-off of 3.2 ng.ml-1 (95th percentile of levels obtained in benign lung disease), the total sensitivity of the marker was 48%. The best sensitivity was obtained in squamous cell lung cancer (60%). The highest values of CYFRA 21-1 were found in metastatic lung cancer, and the marker sensitivity was more elevated in stage IIIb and IV. On the other hand, 40% of patients with surgically resectable lung cancer had CYFRA 21-1 levels above the cut-off. We conclude that CYFRA 21-1 may be satisfactorily employed in the differential diagnosis between malignant and benign lung diseases in association with other clinical and radiological data.

Topics: Biomarkers, Tumor; Carcinoma, Bronchogenic; Diagnosis, Differential; Female; Humans; Immunoradiometric Assay; Keratins; Lung Diseases; Lung Neoplasms; Male; Pulmonary Fibrosis; Sensitivity and Specificity

Cytokeratins are epithelial markers whose expression is not lost during malignant transformation. Cyfra 21-1 is a cytokeratin-19 fragment that is soluble in serum and may be a useful circulating tumor marker.. The aims of this study were (1) to confirm sensitivity and specificity of Cyfra 21-1 in detecting non-small cell lung cancer (NSCLC) and especially the squamous cell subtype, (2) to assess the potential relationship between Cyfra 21-1 and disease stage of the disease in NSCLC, and (3) to evaluate prognostic effect of Cyfra 21-1 in NSCLC.. An immunoradiometric assay of serum Cyfra 21-1 was performed in 161 patients with lung cancers and 71 others with benign lung diseases. The ability of Cyfra 21-1 to detect different histologic subtypes of lung cancer vs benign lung diseases was assessed through receiver operating characteristic (ROC) curves and comparisons with other tumor markers such as carcinoembryonic antigen, neuron-specific enolase, and squamous cell carcinoma antigen. Comparisons of Cyfra 21-1 levels according to histologic subtype and disease stage were done using Kruskal-Wallis test. Independent prognostic value of Cyfra 21-1 was studied with a multivariate analysis of survival (Cox's model).. Using a threshold of 3.3 ng/mL for Cyfra 21-1, sensitivity and specificity were, respectively, 0.59 and 0.94 in NSCLC, 0.68 and 0.94 in the subgroup of the squamous cell carcinoma, and 0.19 and 0.94 in small cell lung cancer. Cyfra 21-1 levels were significantly higher in advanced NSCLC than in early-stage disease. All 29 patients with serum concentrations > 32 ng/mL had stage IIIB-IV and only one of 14 patients with stage I-II disease had Cyfra 21-1 level > 18 ng/mL. In the multivariate analysis of survival, Cyfra 21-1 was an independent prognostic factor along with performance status and disease stage in NSCLC.. Cyfra 21-1 is a sensitive and specific tumor marker of NSCLC, especially of squamous cell subtype. It also reflects the extent of the disease and has an independent prognostic role along with performance status and disease stage in NSCLC.. A high level of Cyfra 21-1 in apparently early-stage NSCLC should be an indication for more extensive workup before thoracotomy. The independent prognostic role of Cyfra 21-1 level may be useful in stratifying populations with advanced NSCLC or early-stage resected NSCLC as elevated Cyfra 21-1 levels might identify those patients at high risk for treatment failure.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Female; Humans; Immunoradiometric Assay; Keratins; Lung Diseases; Lung Neoplasms; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; ROC Curve; Sensitivity and Specificity

The levels of the new tumour marker CYFRA 21-1 were assessed in 115 patients with non-small cell lung cancer (NSCLC) and in 45 patients with non-malignant lung disease. Increased levels of CYFRA 21-1 were observed in 47.8%, mostly in patients with squamous cell carcinoma (SCC; 69.1%). Serum CYFRA 21-1 levels were correlated with the stage of SCC type. Positive CYFRA 21-1 levels in patients with SCC were present in 40% of stage I, 61.1% of stage II, and 85.2% of stage III. In addition, SCC patients who presented mediastinal lymph nodes (N2) demonstrated higher serum CYFRA 21-1 levels, compared with patients without mediastinal lymph nodes metastases (N0 or N1). With regard to tumour size, significant difference was observed between T1, T2 and T3. The study also showed that the percentage of patients who survived 18 months with normal preoperative level of CYFRA 21-1 was higher compared with those patients with elevated preoperative levels of this marker, but the differences were not statistically significant.

Topics: Adenocarcinoma; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Evaluation Studies as Topic; Female; Humans; Keratins; Lung Diseases; Lung Neoplasms; Lymphatic Metastasis; Male; Neoplasm Staging; Peptide Fragments; Serpins

The present study was designed to determine whether CYFRA 21-1, measuring cytokeratin 19, could be a specific and sensitive tumour marker for non-small cell lung cancer (NSCLC). Serum measurements were made at diagnosis in 2250 patient samples by an immunoradiometric "sandwich type" assay, using two cytokeratin 19 specific monoclonal antibodies. Among healthy individuals (n = 711) and patients with benign lung disease (n = 546), 95 percentiles were 1.2 and 2.95 ng/ml, respectively. Cumulative distribution analysis curves were established. From these data, 3.3 ng/ml gave 96% specificity. Using this cutoff, the sensitivity for small cell lung cancer was 16% (n = 74) compared to 41% for NSCLC (n = 547). In histological sub-groups, sensitivity was 57% for squamous cell lung cancer, 34% for undifferentiated large cell carcinoma and 27% for adenocarcinoma, the level of CYFRA 21-1 was correlated with tumour size and UICC stage. In squamous cell lung cancer, the sensitivity of the squamous cell carcinoma marker was 30%, 25% for carcinoembryonic antigen and 46% for tissue polypeptide antigen, using the same series of samples and cutoffs defined at 96% specificity. In conclusion, CYFRA 21-1 is a sensitive tumour marker for NSCLC, especially squamous cell lung cancer.

Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Humans; Keratins; Lung Diseases; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Neoplasms; Peptide Fragments; Retrospective Studies; Sensitivity and Specificity

Cystic and keratinizing squamous lesions have been observed in rats exposed chronically to a number of particulates. A variety of diagnostic terms have been applied to these pulmonary lesions but no consensus exists as to their most proper morphological classification. In an attempt to obtain a consensus for cystic keratinizing pulmonary lesions produced in rats by Kevlar para-aramid fibrils and TiO2 powder, a panel of medical and veterinary pathologists was invited to participate in a workshop addressing the morphology of the lesions and to reach a consensus on a suitable descriptive diagnostic term. All participants agreed that the cystic keratinizing lesions were not malignant neoplasms. The majority was of the opinion that the lesions were not neoplasms. A minority (3/13) considered the lesions to be benign tumors. The panel considered that the most appropriate morphologic diagnosis for the lesions was "proliferative keratin cyst" (PKC). In addition, the panel agreed on the following descriptive text: "The lesions are cysts lined by a well-differentiated stratified squamous epithelium with a central keratin mass. Growth appears to have occurred by keratin accumulation and by peripheral extension of the metaplastic change into the adjacent alveolar spaces. The lesions are sharply demarcated except in those areas in which there has been extension of metaplasia into adjacent alveoli. The squamous epithelium has few mitotic figures and dysplasia is absent."

Topics: Administration, Inhalation; Animals; Cysts; Female; Keratins; Lung Diseases; Male; Polymers; Rats

Topics: Humans; Keratins; Lung Diseases; Lung Neoplasms; Reagent Kits, Diagnostic; Reference Values; Sensitivity and Specificity

Recently CYFRA 21-1, a new tumour marker measuring a fragment of cytokeratin 19, was introduced and proved to be suitable for the follow-up care and monitoring of the therapy of non-small cell lung carcinomas, especially squamous cell carcinomas of the lung. Besides CYFRA 21-1, there are two other tumour markers available, called tissue polypeptide antigen (TPA) and tissue polypeptide specific antigen (TPS), which also measure different cytokeratins in serum. In a retrospective study we investigated the clinical significance of these 3 cytokeratin markers in lung cancer compared with carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and neuron-specific enolase (NSE). We investigated the sera of 50 healthy persons, 273 patients with various benign diseases and 218 patients with histologically proven lung cancer. In a first step the specificity versus benign diseases of the lung was established for all the markers, and was fixed at 95%. Then the single and combined sensitivities were calculated. CYFRA 21-1 proved to possess the highest sensitivity in lung cancer in general (61%), in non-small cell lung carcinomas (64%), in squamous cell carcinomas (79%), in adenocarcinomas (54%) and in large cell carcinomas (65%). In small cell lung carcinomas, neuron-specific enolase proved again to be the marker of first choice (55%). Combined determinations proved clearly increased sensitivity only for large cell carcinomas (CYFRA 21-1 + TPA: 77%) and for small cell lung carcinomas (CYFRA 21-1 + NSE: 62%).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Female; Gastrointestinal Diseases; Genital Diseases, Female; Humans; Keratins; Lung Diseases; Lung Neoplasms; Male; Peptides; Reference Values; Retrospective Studies; Sensitivity and Specificity; Tissue Polypeptide Antigen

In this study 27 transbronchial biopsy specimens obtained from patients with clinical and/or laboratory features suggestive for sarcoidosis were analysed with conventional morphology and immunohistochemistry comparing the sensitivity and reproducibility of the two methods. A limited panel of monoclonal antibodies recognizing epitopes resistant to conventional fixation and embedment procedures were used (CD45R0, CD68, anti-cheratin, anti-collagen IV). All specimens were independently observed by two different pathologists. On the basis of the recognition of bona-fide noncaseating granulomas, 9 cases were uniformly judged as positive, 10 cases as negative, but 8 cases were considered doubtful. Immunohistochemical analysis reliably demonstrated the presence of epithelioid cells in 3 of these cases and absence in 5. These data suggest that the use of a limited immunohistochemical analysis can significantly improve histological diagnosis of sarcoidosis on small transbronchial biopsies using conventional routine material.

Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biopsy; Collagen; Granuloma; Humans; Immunohistochemistry; Keratins; Leukocyte Common Antigens; Lung; Lung Diseases; Reproducibility of Results; Sarcoidosis, Pulmonary; Sensitivity and Specificity

The histogenesis of localized fibrous tumor of the pleura (LFTP) is controversial. We studied 12 LFTP's by light microscopy; by immunohistochemical staining for cytokeratin (CK), vimentin, muscle-specific actin, desmin, S-100 protein, epithelial membrane antigen (EMA) and factor VIII; by electron microscopy in 6 tumors; and by lung digestion for asbestos bodies in 4 cases. Three histologic patterns occurred in combination: 1) collagenous, 2) cellular and 3) hypocellular/myxoid. Hemangiopericytoma-like foci were prominent in the cellular areas of 9 tumors. Unusual features included diffuse small cells in 3 tumors, microcystic foci in 2, macrocystic areas in 5 and tumor giant cells in 4 tumors. Neoplastic cells in all patterns stained positively for vimentin and actin in 9 and 4 tumors, respectively, and were negative for all other markers. CK and EMA were identified in mesothelial and epithelial invaginations only. Ultrastructurally, neoplastic cells demonstrated intercellular junctions, intermediate or thin filaments, dense bodies and rough endoplasmic reticulum. Basal lamina was focally present in 5 tumors, while tonofilaments, desmosomes and short microvilli were observed in one case. Our results support the conclusion that LFTP is a neoplasm of the multipotential subserosal cell, and usually expresses mesenchymal (fibroblastic/myofibroblastic) differentiation. Coexpression of mesothelial features is rare. Lung asbestos body quantitation in 4 patients suggests that there is no association between LFTP and asbestos exposure.

Topics: Actins; Adult; Aged; Asbestos; Cell Transformation, Neoplastic; Desmin; Factor VIII; Female; Humans; Immunohistochemistry; Keratins; Lung; Lung Diseases; Male; Membrane Glycoproteins; Mesoderm; Mesothelioma; Microscopy, Electron; Middle Aged; Mucin-1; Pleural Neoplasms; Vimentin

An enzyme-linked immunosorbent assay (ELISA) for anti-keratin antibodies was prepared by coating microplates with epidermal keratin purified from the stratum corneum from human foot. Naturally occurring auto-antibodies bind keratin via their f(ab')2 fragment. They were assayed in the serum from 65 healthy people. The serum titer increased significantly with aging. Auto-antibodies stained all the layers of a normal human epidermis whereas an immune serum, prepared by injecting a rabbit with pure human keratin proteins, stained more efficiently the outer layers of the human skin; pre-immune rabbit serum did not stain human skin at all. The lowest anti-keratin activities were observed in serum from patients with squamous cell lung carcinoma and with mesothelioma. The activity was lower in pleural fluid from patients with pleural mesothelioma than in pleural fluid from other types of cancer. This is possibly due to the fixation of autoantibodies onto the pleural tumor or on cell debris arising from the tumor.

Topics: Animals; Antibodies; Autoantibodies; Carcinoma, Squamous Cell; Enzyme-Linked Immunosorbent Assay; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Lung Diseases; Lung Neoplasms; Mesothelioma; Pleural Effusion; Rabbits