lewis-x-antigen and Lung-Neoplasms

Immunohistochemistry is frequently employed to aid the distinction between mesothelioma and pulmonary adenocarcinoma metastatic to the pleura, but there is uncertainty as to which antibodies are most useful. We analysed published data in order to establish sensitivity and specificity of antibodies used to distinguish between these tumours with a view to defining the most appropriate immunohistochemical panel to use when faced with this diagnostic problem.. A systematic analysis of the results of 88 published papers comparing immunohistochemical staining of a panel of antibodies in mesothelioma with epithelioid areas, and pulmonary adenocarcinoma metastatic to the pleura. Results for a total of 15 antibodies were analysed and expressed in terms of sensitivity and specificity. The most sensitive antibodies for identifying pulmonary adenocarcinoma were MOC-31 and BG8 (both 93%), whilst the most specific were monoclonal CEA (97%) and TTF-1 (100%). The most sensitive antibodies to identify epithelioid mesothelioma were CK5/6 (83%) and HBME-1 (85%). The most specific antibodies were CK5/6 (85%) and WT1 (96%).. No single antibody is able to differentiate reliably between these two tumours. The use of a small panel of antibodies with a high combined sensitivity and specificity is recommended.

Topics: Adenocarcinoma; Antibodies, Neoplasm; Antigens, Neoplasm; Biomarkers, Tumor; Cadherins; Calbindin 2; Carcinoembryonic Antigen; Diagnosis, Differential; Humans; Immunohistochemistry; Lewis X Antigen; Lung Neoplasms; Mesothelioma; Pleural Neoplasms; S100 Calcium Binding Protein G; Sensitivity and Specificity; Thrombomodulin; Vimentin

Topics: Adenocarcinoma; Biomarkers, Tumor; Digestive System Neoplasms; Female; Humans; Lewis X Antigen; Lung Neoplasms; Male; Neoplastic Cells, Circulating; Ovarian Neoplasms; Radioimmunoassay; Reagent Kits, Diagnostic; Reference Values; Specimen Handling

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Humans; Lewis X Antigen; Lung Neoplasms; Peptide Fragments; Peptides; Phosphopyruvate Hydratase; Recombinant Proteins; Serpins

Topics: Biomarkers, Tumor; Female; Humans; Lewis X Antigen; Lung Neoplasms; Ovarian Neoplasms; Pancreatic Neoplasms

Topics: ABO Blood-Group System; Antigens, Tumor-Associated, Carbohydrate; Autoimmunity; Humans; Lewis X Antigen; Lung Neoplasms; Prognosis

In the clinical practice of lung cancer, serum tumor markers are important laboratory tests and their use is wide spread. Among the various markers for lung cancer, the usefulness of CEA, SLX, SCC and NSE has been firmly established. These markers cannot be used routinely to screen for lung cancer but may be used as complementary tools for diagnosing the tumor. Elevated levels of these markers also appear to be useful for monitoring the response to therapy and tumor progression. CYFRA21-1 and ProGRP, new tumor markers with relatively high sensitivity and specificity to lung cancer, were recently developed. These tumor markers may be useful tools for early detection of lung cancer.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Diagnosis, Differential; Gastrointestinal Hormones; Humans; Intermediate Filament Proteins; Keratin-19; Keratins; Lewis X Antigen; Lung Neoplasms; Neoplasm Staging; Peptide Fragments; Peptides; Phosphopyruvate Hydratase; Recombinant Proteins

Three cases of Hodgkin's disease presenting primarily in the lung are described. All 3 patients presented with respiratory symptoms and chest X-rays revealed discrete masses within the lung parenchyma. CT examination of the mediastinum did not reveal regional or generalized lymphadenopathy at the time of diagnosis in 2 of the cases. A diagnosis of Hodgkin's disease was made on open lung biopsies and despite aggressive chemotherapy, 2 patients died within 2 yrs. The histological and immunocytochemical features of these cases were typical of that expected in Hodgkin's disease. However, the stated indolent course of primary pulmonary Hodgkin's disease is not invariable. Those patients with bilateral interstitial disease and systemic symptoms have a poor prognosis. Furthermore, it is difficult to exclude definitely lymph node involvement (although not enlarged) at the time of diagnosis. Since several cases described in the literature have concurrent and/or subsequent nodal involvement, the entity of primary pulmonary Hodgkin's disease without lymph node involvement is exceedingly rare.

Topics: Adult; Female; Hodgkin Disease; Humans; Lewis X Antigen; Lung Neoplasms; Male; Middle Aged; Reed-Sternberg Cells

Recently many monoclonal antibodies are applied in the clinical diagnosis of human cancers. Most of the antigens recognized by these monoclonal antibodies are carbohydrate in their chemical nature. Among these carbohydrate antigens, the sialyl SSEA-1 antigen is particularly useful for the diagnosis of lung cancers, as the elevated serum level of the sialyl SSEA-1 antigen is frequently observed in patients with adenocarcinoma of the lung (ca. 45-75%). Some of the other carbohydrate antigens, such as CA19-9, are also known to be useful for the diagnosis of lung cancers. These carbohydrate antigens are preferentially found in the sera of patients with adenocarcinoma of the lung, while the SCC antigen (TA-4) is closely associated with squamous cell carcinoma of the lung, and NSE (neuron-specific enolase) is frequently detected in the sera of patients with small cell carcinoma of the lung. The specific serum diagnosis of lung cancer of each histological type is now feasible because of the development of these appropriate tumor markers.

Topics: Animals; Antibodies, Monoclonal; Antigens, Neoplasm; Biomarkers, Tumor; CA-19-9 Antigen; Cricetinae; Humans; Lewis X Antigen; Lung Neoplasms; Phosphopyruvate Hydratase; Serologic Tests

Surgical specimens of 7 cases of bronchioalveolar carcinoma complicated with pulmonary fibrosis and 4 cases of simple pulmonary fibrosis were examined histopathologically and immunohistochemically. The morphology and histogenesis of adenomatous hyperplasia (AH) of alveolar epithelium and its relation to bronchioalveolar carcinoma were investigated. The AH was classified as types I and II according to their microscopic morphologic characteristics. In this group, 6 cases of type I-AH and 5 cases of type II-AH were observed. The results of anti-SA, anti-SSEA-1 and anti-CEA monoclonal antibody examinations indicate that AH is a nonspecific hyperplastic lesion of alveolar epithelium occurred during chronic pulmonary inflammatory diseases. Both type I and II AH originated from type B alveolar epithelial cells. The latter developed on the basis of the former, but with a more immature tendency and hyperplastic potential, being a pre-malignant alteration. It could be considered that certain cases of bronchioalveolar carcinoma are originated from type B alveolar epithelial cells, some of which underwent malignant change from type II alveolar hyperplasia.

Topics: Adenocarcinoma, Bronchiolo-Alveolar; Aged; Apoproteins; Carcinoembryonic Antigen; Epithelium; Female; Humans; Hyperplasia; Immunohistochemistry; Lewis X Antigen; Lung Neoplasms; Male; Middle Aged; Precancerous Conditions; Pulmonary Alveoli; Pulmonary Fibrosis; Pulmonary Surfactant-Associated Proteins; Pulmonary Surfactants

As an important glycosyltransferase, fucosyltransferase IV (FUT4) is abnormally upregulated in different types of cancers, but its clinical role remains inexplicit. This work aimed to determine the predictive ability of FUT4 in lung adenocarcinoma (LUAD) after curative resection, as well as to explore the role of a possible FUT4 molecular mechanism on LUAD malignant behavior.. A total of 273 LUAD patients after curative resection with complete clinicopathological and RNAseq data from The Cancer Genome Atlas (TCGA) cohort were collected. Correlation of FUT4 with overall survival (OS) was analyzed based on TCGA and further validated by online "Kaplan-Meier Plotter" database and IHC in 70 LUAD patients recruited in the First Hospital of China Medical University cohort. Multivariate Cox regression analysis and 1000 bootstrapping were performed to verify the predictive value of FUT4. Gene set enrichment assay (GSEA) was performed to investigate the biological characteristics. Correlation between PD-1 and FUT4 was analyzed based on TCGA cohort and validated by IHC on cohort from our hospital.. Increased FUT4 expression led to reduced overall survival (OS) of LUAD patients based on TCGA (p = 0.006 and 0.001 for dichotomous and trichotomous modeling, respectively) and externally validated in KMPLOTTER (p = 0.01) and by IHC based on cohort from our hospital (p = 0.005 and p = 0.019 for dichotomous and trichotomous modeling, respectively). FUT4 overexpression was an independent high risk factor for OS along with advanced pT stage and pTNM stage (p = 0.001, p = 0.037, and p < 0.001, respectively). GSEA revealed that FUT4 overexpression might correlate with shortened survival of LUAD patients by promoting cell proliferation via ERBB signaling, and suppressing immune response-related pathways. FUT4 expression positively correlated with PD-1 in TCGA (p = 0.026) and validated by IHC on cohort from our hospital (p = 0.029).. Increased FUT4 expression led to reduced OS in operable LUAD. FUT4 showed significant correlation with immune response and PD-1 expression.

Topics: Adenocarcinoma of Lung; Adult; Aged; Aged, 80 and over; Cohort Studies; Female; Fucosyltransferases; Humans; Immunohistochemistry; Lewis X Antigen; Lung Neoplasms; Male; Middle Aged; Prognosis; Programmed Cell Death 1 Receptor; Proto-Oncogene Proteins; Reproducibility of Results; Signal Transduction; Survival Analysis

Metastatic non-small cell lung (NSCLC) cancer represents one of the most common types of brain metastasis. The mechanisms involved in how circulating cancer cells transmigrate into brain parenchyma are not fully understood. The aim of this work was to investigate the role of fucosylated carbohydrate epitopes CD15 and sialyated CD15s in cancer adhesion to brain-derived endothelial cells and determine their influence in blood-brain barrier (BBB) disruption METHODS: Three distinct, independent methods were used to measure brain endothelial integrity and include voltohmmeter (EVOM™), impedance spectroscopy (CellZscope®) and electric cell-substrate impedance sensing system (ECIS™). Two fucosyltransferases (FUT4 and 7) responsible for CD15 and CD15s synthesis were modulated in four human cancer cell lines (three lung cancer and one glioma).. Overexpression of CD15 or CD15s epitopes led to increase in adhesion of cancer cells to cerebral endothelial cells compared with wild-type and cells with silenced CD15 or CD15s (p < 0.01). This overexpression led to the disruption of cerebral endothelial cell monolayers (p < 0.01). Knockdown of FUT4 and FUT7 in metastatic cancer cells prevented disruption of an in vitro BBB model. Surprisingly, although the cells characterised as 'non-metastatic', they became 'metastatic' -like when cells were forced to over-express either FUT4 or FUT7.. Results from these studies suggest that overexpression of CD15 and CD15s could potentiate the transmigration of circulating NSCLC cells into the brain. The clinical significance of these studies includes the possible use of these epitopes as biomarkers for metastasis.

Topics: Blood-Brain Barrier; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Cell Adhesion; Cell Movement; Endothelial Cells; Fucosyltransferases; Humans; Lewis X Antigen; Lung Neoplasms; Tumor Cells, Cultured

Tumor-associated macrophages (TAMs) are key components of tumor microenvironment (TME) during tumorigenesis and progression. However, the role of TAMs in lung adenocarcinoma is still unclear. In this study, we aimed to clarify the mechanism underlying the crosstalk between TAMs and epithelial-mesenchymal transition (EMT) of lung adenocarcinoma. Fucosyltransferase IV (FUT4) and its synthetic cancer sugar antigen Lewis Y (LeY) was aberrantly elevated in various solid tumors, it plays critical role in the invasion and metastasis. Here, we found that in lung adenocarcinoma samples, the density of TAMs correlates with E-cadherin level and LeY level. In vitro assays, M2 macrophages promoted FUT4/LeY expression through the transforming growth factor-β1(TGF-β1)/Smad2/3 signaling pathway. FUT4/LeY was indispensable in M2 macrophages-mediated cytoskeletal remodeling and EMT. Furthermore, fucosylation of Ezrin mediated by FUT4/LeY can promote the phosphorylation of Ezrin, which was the critical mechanism of M2 macrophages-induced EMT. In vivo assays confirmed that M2 macrophages promoted EMT through the up-regulation of LeY and phosphorylated Ezrin. Together, our results revealed that TAMs promote Ezrin phosphorylation-mediated EMT in lung adenocarcinoma through FUT4/LeY- mediated fucosylation. Targeting this newly identified signaling may offer new possibilities for immunotherapy in lung adenocarcinoma.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Animals; Biomarkers; Cadherins; Cell Count; Cell Line, Tumor; Cytoskeletal Proteins; Cytoskeleton; Disease Models, Animal; Epithelial-Mesenchymal Transition; Female; Fucosyltransferases; Heterografts; Humans; Lewis Blood Group Antigens; Lewis X Antigen; Lung Neoplasms; Macrophages; Mice; Models, Biological; Phosphorylation; Signal Transduction; Smad2 Protein; Smad3 Protein; Transforming Growth Factor beta1; Up-Regulation

CD15, which is overexpressed on various cancers, has been reported as a cell adhesion molecule that plays a key role in non-CNS metastasis. However, the role of CD15 in brain metastasis is largely unexplored. This study provides a better understanding of CD15/CD62E interaction, enhanced by tumor necrosis factor-α (TNF-α), and its correlation with brain metastasis in non-small cell lung cancer (NSCLC).. CD15 and E-selectin (CD62E) expression was demonstrated in both human primary and metastatic NSCLC cells using flow cytometry, immunofluorescence, and Western blotting. The role of CD15 was investigated using an adhesion assay under static and physiological flow live-cell conditions. Human tissue sections were examined using immunohistochemistry.. CD15, which was weakly expressed on hCMEC/D3 human brain endothelial cells, was expressed at high levels on metastatic NSCLC cells (NCI-H1299, SEBTA-001, and SEBTA-005) and at lower levels on primary NSCLC (COR-L105 and A549) cells (P < .001). The highest expression of CD62E was observed on hCMEC/D3 cells activated with TNF-α, with lower levels on metastatic NSCLC cells followed by primary NSCLC cells. Metastatic NSCLC cells adhered most strongly to hCMEC/D3 compared with primary NSCLC cells. CD15 immunoblocking decreased cancer cell adhesion to brain endothelium under static and shear stress conditions (P < .0001), confirming a correlation between CD15 and cerebral metastasis. Both CD15 and CD62E expression were detected in lung metastatic brain biopsies.. This study enhances the understanding of cancer cell-brain endothelial adhesion and confirms that CD15 plays a crucial role in adhesion in concert with TNF-α activation of its binding partner, CD62E.

Topics: Blotting, Western; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Cell Adhesion; Cell Line, Tumor; E-Selectin; Endothelial Cells; Flow Cytometry; Fluorescent Antibody Technique; Humans; Lewis X Antigen; Lung Neoplasms; Microscopy, Confocal; Neoplasm Invasiveness; Tumor Necrosis Factor-alpha

The epithelial-mesenchymal transition (EMT) is an important factor in lung cancer metastasis, and targeting EMT is a potential therapeutic strategy. Fucosyltransferase IV (FUT4) and its synthetic cancer sugar antigen Lewis Y (LeY) was abnormally elevated in many cancers. In this study, a traditional Chinese medicine ginsenoside Rg3 was used to investigate whether its inhibition to EMT and invasion of lung cancer is by the glycobiology mechanism. We found that Rg3 treatment (25, 50, 100 μg/ml) inhibited cell migration and invasion by wound-healing and transwell assays. Rg3 could significantly alter EMT marker proteins with increased E-cadherin, but decreased Snail, N-cadherin and Vimentin expression. Rg3 also down-regulated FUT4 gene and protein expression in lung cancer cells by qPCR, Western blot and immunofluorescence. After FUT4 down-regulated with shFUT4, EMT was obviously inhibited. Furthermore, the activation of EGFR through decreased LeY biosynthesis was inhibited, which blocked the downstream MAPK and NF-κB signal pathways. In addition, Rg3 reduced tumor volume and weight in xenograft mouse model, and significantly decreased tumor metastasis nodules in lung tissues by tail vein injection. In conclusion, Rg3 inhibits EMT and invasion of lung cancer by down-regulating FUT4 mediated EGFR inactivation and blocking MAPK and NF-κB signal pathways. Rg3 may be a potentially effective agent for the treatment of lung cancer.

Topics: A549 Cells; Animals; Blotting, Western; Cadherins; Cell Movement; Down-Regulation; Epithelial-Mesenchymal Transition; Fucosyltransferases; Gene Expression Regulation, Neoplastic; Ginsenosides; Humans; Immunohistochemistry; Lewis X Antigen; Lung Neoplasms; Male; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Vimentin; Xenograft Model Antitumor Assays

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature cells of myeloid origin whose expression is induced by, among others things, vascular endothelial growth factor. We have previously identified two monocytic and one granulocytic MDSC subpopulations associated with the clinical outcome in patients with non-small cell lung cancer (NSCLC). The aim of the present study was to evaluate the effect of chemotherapy on these MDSC subpopulations.. Circulating immune cells from 46 patients with unresectable NSCLC were analyzed by flow cytometry before the initiation of chemotherapy and after three cycles. Changes in the frequencies of the MDSC subpopulations were correlated with clinical outcome.. Chemotherapy had no uniform effect on either the number or the functionality of monocytic and granulocytic MDSCs. However, three cycles of bevacizumab-containing regimens significantly reduced the percentage of the granulocytic-MDSCs compared with non-bevacizumab-based regimens (p = 0.0086). At the time of evaluation of response, disease progression was associated with significantly higher levels of all three MDSC subpopulations compared with in patients with disease control. Ιn patients with disease progression after three cycles of chemotherapy, the percentage of CD15-positive monocytic MDSCs was significantly increased compared with baseline.. In the peripheral blood of patients with NSCLC, bevacizumab-based chemotherapy significantly reduced the levels of granulocytic MDSCs. An increase in the levels of CD15-positive monocytic MDSCs was associated with poor response to treatment and disease progression, providing evidence of their clinical relevance in patients with NSCLC.

Topics: Aged; Aged, 80 and over; Bevacizumab; Carcinoma, Non-Small-Cell Lung; Female; Humans; Immunosuppressive Agents; Lewis X Antigen; Lipopolysaccharide Receptors; Lung Neoplasms; Male; Middle Aged; Myeloid-Derived Suppressor Cells; Reactive Oxygen Species

We have recently elucidated a novel function for CD82 in E-cadherin-mediated homocellular adhesion; due to this function, it can inhibit cancer cell dissociation from the primary cancer nest and limit metastasis. However, the effect of CD82 on selectin ligand-mediated heterocellular adhesion has not yet been elucidated. In this study, we focused on the effects of the metastasis suppressor CD82/KAI1 on heterocellular adhesion of cancer cells to the endothelium of blood vessels in order to further elucidate the function of tetraspanins. The over-expression of CD82 in cancer cells led to the inhibition of experimentally induced lung metastases in mice and significantly inhibited the adhesion of these cells to human umbilical vein epithelial cells (HUVECs) in vitro. Pre-treatment of the cells with function-perturbing antibodies against sLea/x significantly inhibited the adhesion of CD82-negative cells to HUVECs. In addition, cells over-expressing CD82 exhibited reduced expression of sLea/x compared to CD82-negative wild-type cells. Significant down-regulation of ST3 β-galactoside α-2, 3-sialyltransferase 4 (ST3GAL4) was detected by cDNA microarray, real-time PCR, and western blotting analyses. Knockdown of ST3GAL4 on CD82-negative wild-type cells inhibited expression of sLex and reduced cell adhesion to HUVECs. We concluded that CD82 decreases sLea/x expression via the down-regulation of ST3GAL4 expression and thereby reduces the adhesion of cancer cells to blood vessels, which results in inhibition of metastasis.

Topics: Animals; Antibodies; beta-Galactoside alpha-2,3-Sialyltransferase; Cell Adhesion; Cell Line, Tumor; Cell Movement; Down-Regulation; Female; Human Umbilical Vein Endothelial Cells; Humans; Kangai-1 Protein; Lewis X Antigen; Lung Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Oligonucleotide Array Sequence Analysis; Real-Time Polymerase Chain Reaction; RNA, Messenger; RNA, Small Interfering; Sialyl Lewis X Antigen; Sialyltransferases; Transplantation, Heterologous

Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of cells with immunosuppressive properties and might confer to worse prognosis in cancer patients. The presence of phenotypically newly described subpopulations of MDSCs and their association with the clinical outcome were investigated in non-small cell lung cancer (NSCLC) patients. The percentages and correlation between MDSCs and distinct immune cells in the peripheral blood of 110 chemotherapy-naive patients before treatment and healthy controls were investigated using flow cytometry. Two monocytic [CD14(+)CD15(-)CD11b(+)CD33(+)HLA-DR(-)Lin(-) and CD14(+)CD15(+)CD11b(+)CD33(+)HLA-DR(-)Lin(-)] and a granulocytic [CD14(-)CD15(+)CD11b(+)CD33(+)HLA-DR(-)Lin(-)] subpopulations of MDSCs were identified, expressing inducible nitric oxide synthase, and reactive oxygen species, respectively. Increased percentages of both monocytic-MDSCs' subpopulations were inversely correlated to dendritic/monocyte levels (P ≤ 0.04), while granulocytic-MDSCs were inversely correlated to CD4(+) T cells (P = 0.006). Increased percentages of monocytic-MDSCs were associated with worse response to treatment (P = 0.02) and patients with normal levels of CD14(+)CD15(+)CD11b(+)CD33(+)HLA-DR(-)Lin(-) had longer overall survival and progression free-survival compared to those with high levels (P = 0.008 and P = 0.005, resp.). Multivariate analysis revealed that the increased percentages of CD14(+)CD15(+)CD11b(+)CD33(+)HLA-DR(-)Lin(-) MDSCs were independently associated with decreased progression free-survival and overall survival. The data provide evidence that increased percentages of new monocytic-MDSCs' subpopulations in advanced NSCLC patients are associated with an unfavourable clinical outcome.

Topics: Aged; Aged, 80 and over; Carcinoma, Non-Small-Cell Lung; CD11b Antigen; Disease-Free Survival; Female; Flow Cytometry; HLA-DR Antigens; Humans; Immunophenotyping; Lewis X Antigen; Lipopolysaccharide Receptors; Lung Neoplasms; Male; Middle Aged; Monocytes; Multivariate Analysis; Myeloid Cells; Nitric Oxide Synthase Type II; Prognosis; Reactive Oxygen Species; Sialic Acid Binding Ig-like Lectin 3; Treatment Outcome

Pt-(GpG) intrastrand crosslinks are the major DNA adducts induced by platinum-based anticancer drugs. In the cell lines and mouse models, the persistence of these lesions correlates significantly with cell damage. Here we studied Pt-(GpG) DNA adducts in circulating tumour cells (CTC) treated with cisplatin in medium upfront to systemic therapy from patients with advanced non-small-cell lung cancer (NSCLC).. Blood was drawn before systemic treatment and the CD45/CD15-depleted fraction of mononuclear cells was exposed to cisplatin, verified for the presence of CTC by pan-cytokeratin (pCK) staining and immunoanalysed for the level of Pt-(GpG) in DNA.. Immunostaining for pCK, CD45 and subsequently for Pt-(GpG) adducts in the cisplatin-exposed cells (ex vivo) at different time points depicted distinct differences for adduct persistence in CTC between responders vs non-responders.. Pt-(GpG) adducts can be detected in CTC from NSCLC patients and assessing their kinetics may constitute a clinically feasible biomarker for response prediction and dose individualisation of platinum-based chemotherapy. This functional pre-therapeutic test might represent a more biological approach than measuring protein factors or other molecular markers.

Topics: Aged; Carcinoma, Non-Small-Cell Lung; Cisplatin; Dinucleoside Phosphates; DNA Adducts; Humans; Leukocyte Common Antigens; Leukocytes, Mononuclear; Lewis X Antigen; Lung Neoplasms; Middle Aged; Neoplastic Cells, Circulating; Platinum; Tumor Cells, Cultured

Most reports on antibodies that claimed to separate mesothelioma from pulmonary adenocarcinoma originated from academic centers or specialized immunohistochemistry laboratories, but little is known about how such stains perform in general practice laboratories. The Canadian Immunohistochemistry Quality Control program circulates tissue array slides to laboratories across Canada; these are stained and then interpreted by the local laboratory and by a set of experienced reviewers. For Canadian Immunohistochemistry Quality Control run 16, tissue array slides from 16 pulmonary adenocarcinomas and 6 mesotheliomas were stained in 36 different laboratories for CEA, CD15, CK5/6, and calretinin. A total of 736 results (cores) were interpretable. If 3 of 4 staining results concordant with the diagnosis was accepted as definitive, 166/192 (86.4%) mesothelioma cores and 461/544 (84.7%) adenocarcinoma cores were correctly diagnosed. However, if 4 of 4 concordant markers were required, then 93/192 (48.4%) mesothelioma cores and 265/544 (48.7%) adenocarcinoma cores were correctly diagnosed. Only 3/192 (1.6%) mesothelioma cores were incorrectly classified as carcinomas and 8/544 (1.5%) of adenocarcinoma cores incorrectly classified as mesotheliomas on the basis of the immunoprofile (ie, 3 of 4 or 4 of 4 marker results were discordant with the diagnosis). We conclude that, in a study based on results from nonspecialized laboratories, the combination of CEA, CD15, calretinin, and CK5/6, used as a panel, has a very low false-positive rate when separating pulmonary adenocarcinomas from mesotheliomas; however, single negative or incorrect results are common, therefore the panel is only useful diagnostically if 3 of 4 correct results are deemed acceptable for diagnosis.

Topics: Adenocarcinoma; Biomarkers, Tumor; Calbindin 2; Carcinoembryonic Antigen; Diagnosis, Differential; False Positive Reactions; Fucosyltransferases; Humans; Immunohistochemistry; Keratin-5; Keratin-6; Lewis X Antigen; Lung Neoplasms; Mesothelioma; Quality Assurance, Health Care; Reproducibility of Results; S100 Calcium Binding Protein G; Sensitivity and Specificity; Tissue Array Analysis

Immune aberrations have been demonstrated in tumorogenesis, and myeloid-derived suppressor cells (MDSC) have shown to play a pivotal role in mediating immune suppression in animal models of human tumors. In the present study, we explored the clinical relevance of CD11b+/CD14⁻/CD15+/CD33+ MDSCs and the association of MDSCs with CD8+ cytotoxic T lymphocytes in patients with non-small-cell lung cancer (NSCLC).. The population of CD11b+/CD14⁻ cells in peripheral blood mononuclear cells (PBMNC) was determined in 173 patients with NSCLC and 42 control subjects. The expression of CD15, CD33, IL-4R, INF-γR, iNOS and L-arginase were analyzed. Cocultures with CD8+ T lymphocytes and Jurkat cells were developed to determine the impact of MDSCs on the expression of CD3ζ of CD8+ T lymphocytes.. Patients with treatment-naïve, advanced-stage NSCLC (n = 87) had an increased subpopulation of CD11b+/CD14⁻/CD15+/CD33+ cells in the PBMNCs with characteristics of MDSCs (P < 0.0001). The CD11b+/CD14⁻ cells in PBMNC also express IL-4R and INF-γR and can suppress CD3ζ expression in CD8+ T lymphocytes. The subpopulation of CD11b+/CD14⁻ cells in PBMNC was decreased in the advanced-stage NSCLC patients who had responsiveness to chemotherapy (n = 41, P < 0.0001) and in the early-stage NSCLC patients after removal of tumor (n = 8, P = 0.0391). Notably, a negative association existed between the population of CD11b+/CD14⁻ cells in PBMNC and the frequency of CD8+ T lymphocytes (n = 48, r = -0.3141, P = 0.0297).. Our study provided evidence of an increased pool of CD11b+/CD14⁻/CD15+/CD33+ MDSCs in the peripheral blood of NSCLC patients. For the suppressive effect of the cells on CD8+ T lymphocytes, these findings suggest the important role of the CD11b+/CD14⁻/CD15+/CD33+ MDSCs in mediating immunosuppression in NSCLC.

Topics: Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Arginase; Blood Cell Count; Blotting, Western; Carcinoma, Non-Small-Cell Lung; CD11b Antigen; CD8-Positive T-Lymphocytes; Cells, Cultured; Coculture Techniques; Female; Flow Cytometry; Humans; Jurkat Cells; Leukocytes, Mononuclear; Lewis X Antigen; Lipopolysaccharide Receptors; Lung Neoplasms; Male; Middle Aged; Myeloid Cells; Neoplasm Staging; Nitric Oxide Synthase Type II; Sialic Acid Binding Ig-like Lectin 3; T-Lymphocytes, Cytotoxic

Topics: Biomarkers, Tumor; Female; Humans; Lewis X Antigen; Lung Neoplasms; Male; Ovarian Neoplasms; Pancreatic Neoplasms; Sialyl Lewis X Antigen

Lung segmentectomy is generally considered as a standard procedure in general thoracic surgery. Anatomical variations of pulmonary segmentation may, however, make it difficult to determine the precise area of resection during segmentectomy. Incomplete pulmonary sub-lobar resection may produce unusual radiographic features. Herein, we report a case of bronchial atresia after lung segmentectomy.

Topics: Aged; Bronchial Diseases; Bronchoscopy; Female; Humans; Lewis X Antigen; Lung Neoplasms; Mucus; Pneumonectomy; Radiography, Thoracic; Thoracic Surgery, Video-Assisted; Thoracotomy; Tomography, X-Ray Computed

Sialyl Lewis antigens (sLe(x/a)) are cancer-associated carbohydrate determinants, serve as ligands of the selectin family and are associated with hematogenous metastasis of cancer. So far, the clinicopathologic values of sialyl Lewis x (sLe(x)) and sialyl Lewis a (sLe(a)) in lung cancer have remained controversial. Using immunohistochemistry, the expressions of sLe(x) and sLe(a) antigens, and an airway mucin (MUC5AC) protein, which was supposed to be the major carrying protein of sialyl Lewis moieties, were studied in surgically resected tumor tissues of 61 patients with stages I or II NSCLC. Thirty-two (52.5%) of the 61 studied subjects were found to be positive for expression of sLe(a), 40 (65.6%) were positive for expression of sLe(x), and 16 (26.2%) were positive for MUC5AC protein. Both the expression of sLe(x) and MUC5AC were associated with adenocarcinoma subtype. Patients bearing tumors with MUC5AC and/or sLe(x) expression had a higher probability of post-operative distant metastasis. Survival analysis demonstrated that patients bearing tumors with expression of sLe(x) antigen or MUC5AC had shorter overall survival. The multivariate logistic regression showed that age >65 years old (OR = 0.207, 95% CI = 0.075-0.569, P = 0.002), nodal status (OR = 6.575, 95% CI = 2.459-17.583, P < 0.001), and MUC5AC (OR = 5.545, 95% CI = 1.998-15.386, P = 0.001) were independent factors affecting survival. We concluded that the expression of sLe(x) was related to MUC5AC protein, while patients with tumors co-expressing both MUC5AC and sLe(x) antigen had the worst survival.

Topics: Adult; Aged; CA-19-9 Antigen; Carcinoma, Non-Small-Cell Lung; Female; Follow-Up Studies; Gangliosides; Gene Expression Profiling; Humans; Immunohistochemistry; Lewis X Antigen; Lung Neoplasms; Male; Middle Aged; Mucin 5AC; Mucins; Multivariate Analysis; Neoplasm Staging; Prognosis; Survival Analysis

The distinction of bronchioloalveolar carcinoma (BAC) from atypical adenomatous hyperplasia (AAH) or reactive alveolar cell hyperplasia (RAH) can be difficult on aspiration cytology, even when cell block preparations are available. The authors evaluated the usefulness of B72.3, carcinoembryonic antigen (CEA), and Leu M-1 immunostains in differentiating BAC, AAH, and RAH.. Immunostains for B72.3, CEA, and Leu M-1 were performed on cell block sections from 11 lung lesions that were diagnosed cytologically as BAC (6 lesions) and "atypical cells, cannot exclude BAC" (5 lesions). Ten histologic sections of AAH and 8 histologic sections of RAH also were stained.. Among the six lesions that had an unequivocal cytologic diagnosis of BAC, all sections were positive for two of three immunostains. Tissue follow-up confirmed BAC in all six lesions. Among the five lesions that were diagnosed as "atypical cells, cannot exclude BAC," four lesions were positive for two of three immunostains, and one lesion was negative for all three immunostains. Subsequent tissue follow-up confirmed BAC in four of these lesions. Follow-up histology of the wedge resection on the lesion in the atypical category that was negative for B72.3, CEA, and Leu M-1 showed only AAH. All 10 lesions that had a histologic diagnosis of AAH and 8 lesions that had a histologic diagnosis RAH were negative for B72.3, CEA, and Leu M-1.. Positive staining for at least 2 immunostains among B72.3, CEA, and Leu M-1 provided strong supportive evidence for the diagnosis of BAC, and a negative result for all 3 immunostains was helpful in excluding BAC and in differentiating BAC from AAH and RAH.

Topics: Adenocarcinoma, Bronchiolo-Alveolar; Antibodies, Neoplasm; Biomarkers, Tumor; Biopsy, Fine-Needle; Carcinoembryonic Antigen; Diagnosis, Differential; Humans; Lewis X Antigen; Lung Neoplasms

Topics: Adult; Diagnosis, Differential; Female; Histiocytoma, Malignant Fibrous; Histiocytosis, Langerhans-Cell; Histiocytosis, Sinus; Hodgkin Disease; Humans; Ki-1 Antigen; Lewis X Antigen; Lung; Lung Neoplasms; Lymph Nodes

Serum tumor marker measurement in addition to radiological examination is useful to detect postoperative recurrence and metastasis. Surgically treated 8 primary non-small cell lung cancer patients who showed negative serum tumor marker postoperatively elevated their markers temporally. Five of the 8 patients did not show recurrence or metastasis in their last confirmation days. These 5 patients had inflammatory disease when the postoperative marker became positive temporally. Remaining 3 patients did not have inflammatory disease when the marker elevated temporally. The marker of the 3 patients became negative again, however, the 3 patients showed recurrence or metastasis during 1 year after temporally elevated day. In conclusion, if there is no inflammatory disease when the negative marker becomes positive temporally, the recurrence or metastasis may be observed during 1 year after temporally elevated day. And when the recurrence or metastasis is observed radiologically, the marker may become negative.

Topics: Adult; Aged; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Non-Small-Cell Lung; Humans; Lewis X Antigen; Lung Neoplasms; Lymph Node Excision; Male; Middle Aged; Pneumonectomy; Postoperative Period

Serum tumor markers are non-invasive diagnostic tools for malignant tumor and commonly used for screening of cancer and as an indicator of treatment-effect. In small cell lung cancer, NSE and proGRP are effective markers. In non-small cell lung cancer (NSCLC), CEA, SCC, CYFRA21-1, SLX and CA19-9 are commonly used for screening, and at least one marker among CEA, SCC or CYFRA21-1 is positive in 77% of patients with NSCLC. According to the histological type, the positive rate of CEA and CYFRA21-1 is high in adenocarcinoma patients, and the positive rate of CYFRA21-1 and SCC is high in squamous cell carcinoma patients. This review summarizes the clinical usefulness of tumor markers in primary lung cancer.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; CA-19-9 Antigen; Carcinoembryonic Antigen; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Humans; Keratin-19; Keratins; Lewis X Antigen; Lung Neoplasms; Peptide Fragments; Peptides; Recombinant Proteins; Serpins

We report a rare case of primary pulmonary Hodgkin's lymphoma associated with Epstein-Barr virus (EBV) and cytomegaly virus (CMV) infections as demonstrated by in situ hybridisation method. Reed-Sternberg cells were CD30 positive. Numerous CD15+ cells were noticed, some of them with concomitant CMV infection.

Topics: Cytomegalovirus; Cytomegalovirus Infections; Diagnosis, Differential; Epstein-Barr Virus Infections; Female; Herpesvirus 4, Human; Hodgkin Disease; Humans; Immunohistochemistry; In Situ Hybridization; Ki-1 Antigen; Lewis X Antigen; Lung Neoplasms; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, T-Cell; Middle Aged; Reed-Sternberg Cells; Tomography, X-Ray Computed

The expressions of three X series Lewis antigens, including Lewis X (Le(x)), sialyl Lewis X (SLe(x)) and sialyl dimeric Lewis X (SDLe(x)) were studied with immuno-histochemical methods in human non-small cell pulmonary cancer (NSCPC) and primary liver cancer (PLC) with different pathological conditions. The Lewis antigens are mainly expressed on the cell surfaces, medially or slightly in the cytoplasm, but not in the cell nuclei of the cancer tissues. The regions adjacent to the cancer tissues do not express any Lewis antigens. The positive rates of these antigens in NSCPC were within the range of 75% to approximately 86%. There was no apparent difference in positive rates between the cases with different differentiation and the presence or absence of metastasis in peripheral lymph nodes, nor among the three antigens, except that the positive rate of SDLe(x) was lower (about 56%) in the cases with well/medium differentiation and without metastasis. However, the expression-intensities (SI indexes) of all three antigens were significantly higher in the samples of poor differentiation and with metastasis as compared to those with well/medium differentiation and without metastasis. The two sialyl Lewis antigens increased more significantly than non-sialylated Le(x). The expressions of these antigens were also observed in the peripheral lymph nodes with metastasis, but not in those without metastasis. The positive rates of Le(x), SLe(x) and SDLe(x) in human primary liver cancer were 83.3%, 88.9% and 77.8%, respectively. In the cases with cancer cell thrombosis (CCT) in portal vein (an index of metastasis), the expressions of all these three antigens were stronger than those in the cases without CCT. SLe(x) was the most abundant and most highly increased Lewis antigen on the surface of NSCPC and PLC, especially in the cases with poor differentiation and metastasis. In the study of the enzymatic basis of the increased Lewis antigens in PLC by using Northern blot, it was found that the level of alpha1,3 FucT-III/VI mRNA in PLC tissues was much higher than that in the adjacent regions, and more significantly higher in the cancer tissues from patients with CCT in portal vein. In contrast, the expression of alpha1,3 FucT-VII was rather low in cancer tissues and not different from the adjacent regions in spite of the presence or absence of CCT. These results reveal that the SLe(x) in PLC is mainly synthesized by alpha1,3 FucT-III/VI (especially VI) and is the most im

Topics: Carcinoma, Non-Small-Cell Lung; Humans; Lewis X Antigen; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Neoplasm Staging

Making a preoperative pathologic diagnosis in patients with small lung nodules remains challenging. We have developed a new, noninvasive bronchoscopic microsampling probe to examine biochemical substances in epithelial lining fluid. We used this probe to measure tumor markers in fluid from tissues surrounding lung nodules less than 30 mm in diameter to test its adjunctive diagnostic utility in lung cancer.. In 12 patients, epithelial lining fluid was collected in triplicate or duplicate from tissue within 2 cm of small peripheral lung nodules and from the contralateral lung. The diagnosis of adenocarcinoma was surgically confirmed in all patients. Fifteen patients without lung cancer served as controls. Concentrations of carcinoembryonic antigen, cytokeratin fragment 19, and sialyl SSEA-1 were measured in the fluid.. Carcinoembryonic antigen and cytokeratin fragment 19 concentrations were significantly higher in fluid near the nodules (median, 8.7 and 87.2 ng/mg, respectively) than on the contralateral sides (median, 1.5 and 3.7 ng/mg, respectively) or in fluid collected from the controls (median, 2.0 and 2.8 ng/mg, respectively).. Measurements of carcinoembryonic antigen and cytokeratin fragment 19 collected by our microsampling probe may be a useful diagnostic adjunct in patients with small peripheral lung nodules.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Biopsy, Needle; Bronchoscopes; Bronchoscopy; Carcinoembryonic Antigen; Case-Control Studies; Equipment Design; Female; Humans; Immunohistochemistry; Keratins; Lewis X Antigen; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Prognosis; Prospective Studies; Sensitivity and Specificity; Treatment Outcome

To evaluate the prognostic relevance of CEACAM1 and sialyl Lewis X expression in adenocarcinomas of the lung.. Paraffin wax sections of 93 patients with adenocarcinomas of the lung who underwent surgery between 1990 and 1995 were immunohistochemically investigated using monoclonal anti-CEACAM1 and sialyl Lewis X antibodies. The clinical course of all patients was followed up for a minimum of 5 years.. Sixty-one tumors were classified as CEACAM1-positive, and 32 were classified as CEACAM1-negative. Patients with CEACAM1-positive tumors had a significantly poorer overall (P =.00025) and relapse-free (P =.00029) survival than those with CEACAM1-negative tumors. Only three patients did not express the sialyl Lewis X glycotope, whereas 90 tumors (97%) were sialyl Lewis X-positive. In multivariate Cox regression analysis, next to tumor stage and sex, only the expression of CEACAM1 was a significant independent prognostic factor for survival.. Expression of CEACAM1 was an independent prognostic factor in our patient population and can be used to stratify patients with adenocarcinomas of the lung into low-risk and high-risk groups. In contrast, the expression of sialyl Lewis X was of no prognostic relevance because it was expressed in 97% of all investigated tumors, and most likely has no influence on the function of CEACAM1 in this tumor entity.

Topics: Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal; Antigens, CD; Antigens, Differentiation; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Cell Adhesion Molecules; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Lewis Blood Group Antigens; Lewis X Antigen; Lung Neoplasms; Male; Middle Aged; Oligosaccharides; Prognosis; Retrospective Studies; Risk Factors; Sialyl Lewis X Antigen; Survival Analysis

The distinction between pleural epithelial mesothelioma and peripheral lung adenocarcinoma involving the pleura is still an important diagnostic problem for surgical pathologists. The aim of our study was to identify the most specific and sensitive markers for the positive identification of mesothelioma to select a limited, appropriate panel of antibodies to differentiate between mesothelioma and adenocarcinoma. Forty-two cases of epithelial mesotheliomas and 23 cases of pulmonary adenocarcinomas were stained with the following antibodies: anticalretinin, antithrombomodulin, anti-CD44H, and monoclonal antibody HBME-1. We also studied the value of other markers in current use: cytokeratins AE1/AE3 and CAM5.2, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), Ber-EP4, B72.3, and CD15. Of the mesotheliomas, 42 stained for calretinin, 39 (92.8%) for thrombomodulin, 42 stained for CD44H, and 41 (97.6%) stained for HBME-1. Among negative markers, 4 (9.5%) mesothelioma cases stained for CEA, 5 (11.9%) stained for Ber-EP4, 6 (14.2%) stained for B72.3, and 2 (4.7%) stained for CD15. Of the lung adenocarcinomas, 2 (8.7%) cases showed reactivity for calretinin, 5 (21.7%) for thrombomodulin, 13 (56.5%) for CD44H, all for HBME-1, 22 (95.6%) for CEA, 22 (95.6%) for Ber-EP4, 8 (34.7%) for B72.3, and all for CD15. In conclusion, calretinin and thrombomodulin were the most specific positive mesothelial markers, whereas CD44H and HBME-1 showed high sensitivity but very low specificity. Among negative markers, we advocate the use of CEA and CD15 which were the most specific in differentiating mesotheliomas from adenocarcinomas.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Calbindin 2; Carcinoembryonic Antigen; Diagnosis, Differential; Humans; Hyaluronan Receptors; Immunohistochemistry; Keratins; Lewis X Antigen; Lung Neoplasms; Mesothelioma; Mucin-1; Pleural Neoplasms; S100 Calcium Binding Protein G; Thrombomodulin

Anti-CEA, anti-vimentin, CAM5.2, BerEp4, Leu-M1 and anti-EMA were applied to effusions from 36 mesotheliomas, 53 adenocarcinomas and 24 reactive mesothelial proliferations. Stepwise logistic regression analysis selected three criteria of major importance for distinguishing between adenocarcinoma and mesothelioma: BerEp4, CEA and EMA accentuated at the cell membrane (mEMA), these three being of similar diagnostic value. The pattern BerEp4-, CEA- and mEMA+ was fully predictive for mesothelioma (sensitivity 47%), whereas the opposite pattern was fully predictive for adenocarcinoma (sensitivity 80%). Only EMA seemed to distinguish between mesotheliosis and mesothelioma. Comparison of reactivity in cytological and histological material from the same mesotheliomas showed similar staining frequencies for CEA and CAM5.2, with some random variation for Leu-M1 and EMA, whereas vimentin and BerEp4 reactivity was more frequent in cytological specimens.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antibodies, Neoplasm; Antibody Specificity; Antigens, Neoplasm; Antigens, Surface; Biomarkers; Biomarkers, Tumor; Carcinoembryonic Antigen; Diagnosis, Differential; Epithelium; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; Lewis X Antigen; Logistic Models; Lung Neoplasms; Mesothelioma; Mucin-1; Neoplasm Proteins; Pleural Effusion, Malignant; Sensitivity and Specificity; Vimentin

To evaluate HBME-1, WT1, calretinin and MOC-31 in the differential diagnosis of pleural mesothelioma and adenocarcinoma of the lung.. Paraffin-embedded formalin-fixed blocks from six reactive pleuras, 42 mesotheliomas and 40 adenocarcinomas were used. Sections were stained for Leu-M1, HBME-1, calretinin, WT1 and MOC-31. Leu-M1 was positive or equivocal in 34% of mesotheliomas and in 78% of adenocarcinomas; reactive pleuras were all negative. HBME-1 was positive or equivocal in 76% of mesotheliomas and in 73% of adenocarcinomas; five reactive pleuras were positive. Calretinin was positive or equivocal in 92% of mesotheliomas and in 73% of adenocarcinomas; two reactive pleura were equivocal and four were positive. WT1 was positive or equivocal in 72% of mesotheliomas (excluding autopsy cases) and in 20% of adenocarcinomas; all reactive pleuras were positive. MOC-31 was positive or equivocal in 5% of mesotheliomas and in 90% of adenocarcinomas; all reactive pleuras were negative. The reaction with Leu-M1 was graded as equivocal in 25% of the adenocarcinomas. All 24 of the autopsy cases of mesothelioma were negative for WT1 and in many operative specimens only the periphery was stained.. Neither calretinin nor HBME-1 are sufficiently discriminatory to be of use, even as members of a panel of antibodies. WT1 shows some promise, but it cannot be used on autopsy material. The utility of MOC-31 is confirmed, and outperforms Leu-M1.

Topics: Adenocarcinoma; Antibodies, Neoplasm; Antigens, Neoplasm; Antigens, Surface; Biomarkers, Tumor; Calcium-Binding Proteins; Calreticulin; Diagnosis, Differential; DNA-Binding Proteins; Evaluation Studies as Topic; Humans; Immunohistochemistry; Lewis X Antigen; Lung Neoplasms; Mesothelioma; Pleural Neoplasms; Ribonucleoproteins; Transcription Factors; WT1 Proteins

Lewis X, Sialyl Lewis X and Sialyl Dimeric Lewis X are three fucosylated glycoconjugates on cell surface. With immunohistochemical method, the expression of the three structures in the original lung cancer tissues (with or without metastasis), adjacent tissues and metastatic lesions of lung carcinoma were studied. It was found that the three antigens were expressed with different intensity on the cell surface and in the cytoplasm of the lung carcinoma cell. However, there was no or only trace expression of these antigens in the adjacent tissues of lung carcinoma and normal lung tissues. Moreover, the original lesions of lung carcinoma with metastasis and/or poor differentiation expressed higher level of the three antigens than those without metastasis and/or with well or medium differentiation. Sialyl Lewis X was considered to be more closely related to the metastatic ability and differentiation of the lung carcinoma cell than the other two antigens, Lewis X and Sialyl Dimeric Lewis X. Furthermore, in the lymph nodes with lung carcinoma cell metastasis, there were expression of the three antigens with different degree, while in those lymph nodes without lung carcinoma cell metastasis, there was no expression of the three antigens.

Topics: Glycoconjugates; Humans; Immunohistochemistry; Lewis X Antigen; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Oligosaccharides; Sialyl Lewis X Antigen

Aberrant expression of cell surface carbohydrates such as sialyl Lewis X is associated with tumor formation and metastasis. In order to determine the roles of sialyl Lewis X in tumor metastasis, mouse melanoma B16-F1 cells were stably transfected with alpha1, 3-fucosyltransferase III to express sialyl Lewis X structures. The transfected B16-F1 cells, B16-FTIII, were separated by cell sorting into three different groups based on the expression levels of sialyl Lewis X. When these transfected cells were injected into tail veins of C57BL/6 mice, B16-FTIII.M cells expressing moderate amounts of sialyl Lewis X in poly-N-acetyllactosamines produced large numbers of lung tumor nodules. Surprisingly, B16-FTIII.H cells expressing the highest amount of sialyl Lewis X in shorter N-glycans died in lung blood vessels, producing as few lung nodules as B16-FTIII.N cells which lack sialyl Lewis X. In contrast, B16-FIII.H cells formed more tumors in beige mice and NK cell-depleted C57BL/6 mice than did B16-FTIII.M cells. B16-FTIII.H cells bound to E-selectin better than did B16-FTIII.M cells, but both cells grew at the same rate. These results indicate that excessive expression of sialyl Lewis X in tumor cells leads to rejection by NK cells rather than tumor formation facilitated by attachment to endothelial cells.

Topics: Animals; Cell Division; Cytotoxicity, Immunologic; E-Selectin; Flow Cytometry; Fucosyltransferases; Graft Rejection; Killer Cells, Natural; Lewis X Antigen; Lung Neoplasms; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Neoplasm Metastasis; Neoplasm Transplantation; Oligosaccharides; Recombinant Proteins; Sialyl Lewis X Antigen; Transfection; Tumor Cells, Cultured

Sialyl Lewis a and x antigens are well-known tumor-associated antigens expressed in many cancer tissues. The expression of the genes encoding 5 alpha1,3fucosyltransferases, which are able to synthesize the sialyl Lewis antigens, was examined in normal and cancerous lung tissues of patients with non-small cell lung carcinoma. In all 20 cases examined, the transcripts only for the Lewis gene, encoding the Lewis enzyme (alpha1,3/4fucosyltransferase, Fuc-TIII), were abundantly expressed in lung tissue, and interestingly they were markedly up-regulated in the lung cancer tissues of all 20 cases in comparison with normal lung tissues. Myeloid-type alpha1,3fucosyltransferase (Fuc-TIV) was expressed at an intermediate level but was not up-regulated in lung cancer tissues. The transcripts for plasma-type alpha1,3fucosyltransferase (Fuc-TVI) gene were detected at a very low level but were apparently up-regulated in cancer tissues. Fuc-TVI was found to exhibit stronger relative activity for sialyl Lewis x synthesis (almost 6. 4-fold that of Fuc-TIII). The amount of sialyl Lewis x antigen on mucins in the lung cancer tissues was found to be determined by both enzymes, the Lewis enzyme (Fuc-TIII) and Fuc-TVI. However, the amount of the sialyl Lewis a antigens was not determined by any of the alpha1,3-fucosyltransferases, although the expression of sialyl Lewis a antigens definitely required the Lewis enzyme.

Topics: Adenocarcinoma; Aged; Base Sequence; Blotting, Western; Carcinoma, Non-Small-Cell Lung; DNA, Complementary; Epitopes; Female; Fucosyltransferases; Genotype; HeLa Cells; Humans; Immunohistochemistry; Lewis X Antigen; Lung; Lung Neoplasms; Male; Middle Aged; Models, Statistical; Molecular Sequence Data; Reverse Transcriptase Polymerase Chain Reaction; Up-Regulation

Topics: Adenocarcinoma; Biomarkers, Tumor; Humans; Lewis Blood Group Antigens; Lewis X Antigen; Lung Neoplasms; Pleural Effusion, Malignant; ROC Curve

Changes in cell membrane carbohydrate antigens play an important role in metastatic potential associated with carcinogenesis and in prognostic factors. We investigated immunohistochemically the expression of CD15 and sialyl CD15 (sCD15) in lung cancer tissue by using Leu-M1 antibody and MXKM-93 antibody, respectively, and then assessed the relationship between their expression and the patient outcome. Lung cancer tissue expression of CD15 was significantly higher in adenocarcinoma (55.9%) and squamous cell carcinoma (44.7%) than in small cell carcinoma (10%) (p=0.01, p=0.006). Expression of sCD15 was significantly higher in adenocarcinoma (52.9%) than in squamous cell carcinoma (10.5%) or small cell carcinoma (10%) (p<0. 0001, p=0.016). No association was found between CD15 expression and clinical stage, but sCD15 expression increased with clinical stage (stage I+II vs. III+IV: 16.7% vs. 39.6%; p=0.049). Expression of CD15 (1.5%) was significantly lower than expression of sCD15 (12.3%) in normal surrounding tissue. Examination of associations with outcome in NSCLC revealed that expression of sCD15 in resected cases, and expression of CD15 in non-resected cases were significantly correlated with shortening of median survival time (p<0.05). When associations with prognostic factors were assessed by univariate analysis, expression of sCD15 was found to be correlated with distant metastasis, and expression of CD15 with decrease in performance status (PS). In the multivariate analysis by the Cox proportional hazard model, sCD15 and CD15 negativity contributed to longer survival time after PS and clinical stage. The results of a combination assay of CD15 and sCD15 showed that expression of both carbohydrate antigens significantly shortened survival time in both the resected and non-resected group (log-rank test, p<0.05). This combination assay also appeared to be extremely useful in predicting the outcome in all clinical stages of NSCLC.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Animals; Antigens, Tumor-Associated, Carbohydrate; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Disease Progression; Female; Humans; Immunohistochemistry; Lewis X Antigen; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oligosaccharides; Prognosis; Rabbits; Risk Factors; Sialyl Lewis X Antigen; Survival Analysis

Alpha(1,3)- and alpha(1,4)-fucosylated oligosaccharides such as sialyl-Lewis(x) (sialyl-Le(x)) and sialyl-Lewis(a) (sialyl-Le(a)) have been reported to participate in tumor cell adhesion to activated endothelium. We examined by cytofluorometry the expression of Le(x), sialyl-Le(x), sialyl-Le(x) dimeric, Le(a), and sialyl-Le(a) on the surface of two human lung adenocarcinoma cell lines with different lung colonization potential. High expression levels of all of these antigens were detected in the metastatic HAL-8Luc cells, whereas the closely related nonmetastatic HAL-24Luc cells only expressed the sialyl-Le(a) and sialyl-Le(x) dimeric antigens, both at lower level than in HAL-8Luc cells. Five alpha(1,3)-fucosyltransferases (alpha(1,3)-Fuc-T) controlling the synthesis of these molecules have been identified to date (Fuc-TIII-Fuc-IVII). The expression of these five genes was also higher in the metastatic cells than in the nonmetastatic counterparts as was shown by Northern blot analysis. In vitro adhesion assays showed that only the metastatic cell line adheres significantly to E-selectin-expressing human endothelial cells. Moreover, monoclonal antibody (mAb) blockade of E-selectin completely abolished tumor cell binding. Adhesion inhibition experiments using mAbs against sialylated fucosylated oligosaccharides expressed on tumor cells indicated that these antigens are involved in the binding. Anti-sialyl-Lex(x) mAb (CSLEX-1) inhibited adhesion by 85%; it had the most pronounced inhibitory effect. These findings suggest that the overexpression of alpha(1,3)-Fuc-T genes in the metastatic HAL-8Luc cells, compared with HAL-24Luc cells, results in an enhanced surface display of fucosylated oligosaccharides, which contributes to the adhesive capacity of these cells to the activated endothelium and correlates with their lung colonization potential.

Topics: Adenocarcinoma; Animals; Antigens, Neoplasm; Antigens, Surface; Blotting, Northern; CA-19-9 Antigen; Cell Adhesion; E-Selectin; Endothelium; Flow Cytometry; Fucosyltransferases; Gangliosides; Gene Expression; Humans; Lewis X Antigen; Lung Neoplasms; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Metastasis; Oligosaccharides; Sialyl Lewis X Antigen; Tumor Cells, Cultured

The tumor-associated carbohydrate antigens sLe(x) and sLe(a) are known to be ligands of endothelial cell leukocyte adhesion molecule-1 (ELAM-1) and to be involved in hematogenous metastasis of human cancer cells. To determine whether expression of these carbohydrate antigens in lung cancer is associated with metastatic status, we immunohistochemically evaluated the expression of sLe(x) and sLe(a) in 52 bronchofiberscopic biopsy specimens obtained from patients with various stages of previously untreated lung cancer. The incidence of sLe(x) and sLe(a) positivity by immunostaining was 65.4 and 13.4%, respectively (P < 0.01). The incidence of sLe(x) positivity in patients with adenocarcinoma (94.7%) was significantly higher than in patients with squamous cell carcinoma (52.0%) and small cell carcinoma (28.6%) (P < 0.05). The high sLe(x) immunoreactivity correlated with metastasis to a distant organ (P < 0.05), but not with lymph node metastasis. The serum levels of these carbohydrate antigens measured by a serological assay correlated with their immunohistochemically detected expression (P < 0.01). These findings indicate that sLe(x) is expressed more frequently than sLe(a) in bronchofiberscopic biopsy specimens and plays an important role in distant metastasis in lung cancer patients.

Topics: Aged; Aged, 80 and over; Biopsy; Chi-Square Distribution; Female; Humans; Lewis X Antigen; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Radioimmunoassay

To assess the usefulness of sialyl stage-specific embryonic antigen-1 (SSEA-1) levels in differentiating the etiology of pleural effusion (PE).. A solid-phase immunoradiometric sandwich assay with an FH6 monoclonal antibody was used to measure sialyl SSEA-1 levels in PEs of 132 patients with various diseases. Paired serum sialyl SSEA-1 levels were measured simultaneously in 47 patients with various subtypes of lung cancer. The pleural sialyl SSEA-1 levels were significantly higher in patients who had adenocarcinoma of the lung with positive cytology than in all the other patients, including those having malignancies other than adenocarcinoma of the lung, adenocarcinoma of the lung with cytology-negative PE, and benign diseases. There were no significant differences among sialyl SSEA-1 levels in the pleural fluid containing no adenocarcinoma cells. Using the cutoff value of 265 U/mL, the sensitivity was 64% (25/39) and the specificity was 95% (88/93) for the pleural sialyl SSEA-1 level to differentiate adenocarcinoma from other effusions.. With high specificity and modest sensitivity, the pleural sialyl SSEA-1 level is a useful biochemical marker for differentiating the etiology of PEs caused by adenocarcinoma from other diseases.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Female; Humans; Lewis X Antigen; Lung Neoplasms; Male; Middle Aged; Pleural Effusion, Malignant; Sensitivity and Specificity

The most common clinical form of lung cancer is a disseminated disease with distant metastases; several years of cancer progression precede presentation, and this ultimately limits the efficacy of curative therapy. In this immunohistochemical study, we examined a mucinous adenocarcinoma cell line, maintained by xenogeneic transplantation, and a spontaneous metastatic variant which produces distant tumors (in liver, spleen and kidney). The aim was to investigate possible parameters which characterize the metastatic process. Histopathological comparison between the two subcutaneous transplanted tumor lines showed that both lines presented a similar cellular morphology, a different pattern of cellular growth and an increased vascularization in the metastatic line with respect to its parent. All the tumor sections expressed differential immune reactivity with monoclonal antibodies against Lewis y (MAb C14), sialyl-Lewis x (MAb SNH3) and Lewis x (MAb FH2) determinants. Neither expressed MUC 1 mucins detectable with monoclonal antibodies reactive with the mucin protein core (MAbs C595 and SM3) nor was carcinoembryonic antigen (MAb C365) expressed. Neoplastic cells were reactive with an anti-pan cytokeratin monoclonal antibody confirming their epithelial histogenesis. Our findings have been evaluated with respect to defining metastatic phenotypes in lung cancer by examination of distinct histopathological and immunological parameters.

Topics: Adenocarcinoma, Mucinous; Animals; Antibodies, Monoclonal; Apoptosis; Biomarkers, Tumor; Carcinoembryonic Antigen; Cell Nucleus; Cytoplasm; Gangliosides; Humans; Image Processing, Computer-Assisted; Immunoenzyme Techniques; Injections, Subcutaneous; Kidney Neoplasms; Lewis Blood Group Antigens; Lewis X Antigen; Liver Neoplasms, Experimental; Lung Neoplasms; Mice; Mice, Nude; Mucin-1; Mucins; Neoplasm Proteins; Neoplasm Transplantation; Neoplastic Stem Cells; Oligopeptides; Peptide Fragments; Phenotype; Sialyl Lewis X Antigen; Splenic Neoplasms; Transplantation, Heterologous; Tumor Cells, Cultured

Histologic features of recurrent Hodgkin's disease (HD) after conventional therapy are well known, but few studies describe HD after bone marrow transplantation (BMT). Histologic material from 63 patients who underwent BMT performed to treat recurrent nodular sclerosing HD (NSHD) between 1985 and 1994 was examined; 13 of the 63 patients had histologically proved recurrent disease after BMT. Histologic material and clinical findings from the original diagnostic biopsy specimen and pre-BMT and post-BMT specimens were available from our study population of eight patients (five male, three female; age range, 16 to 38 years; median age, 27.5 years). Seven patients had recurrent NSHD after BMT; sites of recurrence included lymph nodes only (four patients), and lymph nodes and lung, lung and liver, and lung only (one patient each). In one patient, a high-grade non-Hodgkin's B-cell lymphoma developed in the large intestine 5 years after BMT. In another, disease progressed from grade 1 in the original biopsy specimen to grade 2 in both the pre-BMT and post-BMT recurrent HD biopsy specimens. Post-BMT biopsy specimens of recurrent HD with lung involvement revealed a substantial increase in sclerosis and fibroblastic features. Paraffin immunoperoxidase studies in seven patients demonstrated substantial change in phenotype of Reed-Stemberg cell variants in only one post-BMT recurrent HD specimen, which showed a +2 reaction with CD30 (Ki-1). No substantial differences in the reactive component were noted between the original biopsy specimen and pre-BMT and post-BMT specimens of recurrent disease. In summary, histologic findings of post-BMT recurrent NSHD do not differ significantly from those of the original diagnostic biopsy or pre-BMT recurrent HD specimens. The lung is the most common site of extranodal post-BMT recurrence. In one patient, high-grade non-Hodgkin's B-cell lymphoma developed after BMT performed to treat recurrent HD.

Topics: Adolescent; Adult; Bone Marrow Transplantation; Female; Hodgkin Disease; Humans; Immunoenzyme Techniques; Ki-1 Antigen; Lewis X Antigen; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Male; Mediastinal Neoplasms; Mucin-1; Necrosis; Recurrence; Sclerosis

Increased glucose transport is a common characteristic of most tumors. To examine the role of elevated glucose uptake in lung cancer, we performed PCR amplification of 2 facilitative glucose transporter genes (GLUT1 and GLUT3) and immunohistochemical staining for GLUT1, proliferating cell nuclear antigen (PCNA), and sialyl Lewis x (sLe(x)) on tumor specimens from 327 patients with lung cancer who underwent surgical resection from 1980 to 1993. To evaluate the relationship between GLUT, alpha-2,3-sialyltransferase (ST), and alpha-1,3-fucosyltransferase (Fuc-T) genes, PCR amplification of the ST3N and Fuc-TVII also was performed. Amplification of GLUT1 was significantly greater than that of GLUT3. GLUT1 and GLUT3 amplification correlated with PCNA staining (p < 0.01). In addition, GLUT1 amplification correlated with the grading of sLe(x) staining as well as with the grading of GLUT1 staining (p < .03, p < 0.01). GLUT1 was co-amplified with ST3N and Fuc-TVII genes, which are involved in the synthesis of sLe(x) (p < 0.01). The survival of patients whose tumors showed GLUT1 amplification was significantly shorter than that of patients whose tumors did not (p < 0.01). In a multivariate analysis of survival, GLUT1 remained a statistically significant prognostic factor. Our results suggest that GLUT1 amplification may participate in sLe(x) synthesis as well as in proliferation, and may be of prognostic value in lung cancer.

Topics: Adult; Aged; Aged, 80 and over; Cell Division; Female; Fucosyltransferases; Gene Amplification; Humans; Lewis X Antigen; Lung Neoplasms; Male; Middle Aged; Monosaccharide Transport Proteins; Multivariate Analysis; Proliferating Cell Nuclear Antigen; Sialyltransferases; Survival Analysis

We report a case of lymphoma associated with lung carcinoma that shows morphological and immunohistochemical features of anaplastic large cell Ki-1 positive lymphoma and Hodgkin's disease, with positivity for Ki-1 (CD-30) (characteristic of both lymphomas) and Leu-M1 (CD-15) (normally dosent absent in anaplastic lymphoma). This subtype of lymphoma is designated anaplastic large-cell Hodgkin's related lymphoma (ALCL related to HD) and is considered by some authors as a secondary anaplastic large-cell lymphoma.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Fatal Outcome; Hodgkin Disease; Humans; Ki-1 Antigen; Ki-67 Antigen; Lewis X Antigen; Lung Neoplasms; Lymphoma, Large-Cell, Anaplastic; Male; Middle Aged; Neoplasms, Multiple Primary

Recently, we have recommended immunocytochemistry on serous effusions with the monoclonal antibodies Ber-EP4 and EMA to be used as a routine procedure. In this study, our earlier defined immunocytochemical profiles were tested in daily diagnostic work for a period and the profiles were applicated on the corresponding cell blocks from the effusions, too. It is concluded that routine use of the benign, malignant epithelial, and malignant mesothelial immunocytochemical profiles is valuable and superior to cytomorphology alone. Additionally, immunocytochemical staining of smears proved slightly more sensitive than immunohistochemistry performed on sections from the cell blocks.

Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Breast Neoplasms; Carcinoma; Carcinoma, Renal Cell; Diagnosis, Differential; Exudates and Transudates; Female; Follow-Up Studies; Humans; Immunohistochemistry; Lewis X Antigen; Lung Neoplasms; Mesothelioma; Ovarian Neoplasms; Paraffin Embedding; Predictive Value of Tests; Vaginal Smears

Topics: Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Humans; Lewis X Antigen; Lung Neoplasms; Prognosis; Survival Rate

Immunohistochemical expression of Lewisy, sialyl Lewisx, and sialyl Lewisa were examined in relation to blood vessel invasion and prognosis in 133 patients with stage I non-small cell lung cancer who had a curative resection from 1980 to 1991. Expression of sialyl Lewisx in adenocarcinomas was higher than in squamous cell and large cell carcinomas, and Lewisy immunoreactivity was the highest among the three antigens. The frequency of blood vessel invasion was significantly higher in tumors with expression of Lewisy or sialyl Lewis antigen (sialyl Lewisx or sialyl Lewisa), however, Lewisy expression was even more significant. The postoperative survival was significantly shorter when tumors expressed both the Lewisy and sialyl Lewis antigen. However, the survival of patients with either Lewisy or sialyl Lewis antigen expression was similar to that of patients whose tumors did not express either the Lewisy or sialyl Lewis antigens. These results suggest that Lewisy and sialyl Lewis antigen may be of prognostic value for metastatic potential but have different functional roles in tumor cells.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antigens, Tumor-Associated, Carbohydrate; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Humans; Lewis X Antigen; Lung Neoplasms; Middle Aged; Prognosis; Survival Rate

SLX levels in the culture supernatant of the following 50 cell lines were measured by RIA: pulmonary carcinoma cell lines derived from 46 patients, cell lines of other human cancers derived from 4 patients, and 2 passaged human fibroblast cells as control. Of the 46 pulmonary carcinoma cell lines, 17 (37%) were SLX positive. When the SLX-positive rate was analyzed in relation to the histological type of pulmonary carcinoma, the positive rate was 71% (10/14) for adenocarcinoma, 27% (3/11) for squamous cell carcinoma, 33% (2/6) for large cell carcinoma, 0% (0/11) for small cell carcinoma and 50% (2/4) for adenosquamous cell carcinoma. Analysis of the relationship between tumor cell proliferation and SLX level in 20 patients revealed that the SLX level in the supernatant of SLX-producing cell lines becomes higher in proportion to the increase in the number of these cells. The SLX-positive rate did not differ significantly among different stages of pulmonary carcinoma at the time of tissue collection. There was no significant correlation between SLX production and prognosis. SLX production by each cell line was not correlated with the doubling time of the same cell line in vitro or in vivo (in nude mice). SLX production also showed no correlation with the duration of tumor cell passage.

Topics: Adult; Aged; Carcinoma; Cells, Cultured; Female; Humans; Lewis X Antigen; Lung Neoplasms; Male; Middle Aged; Radioimmunoassay; Tumor Cells, Cultured

Blood vessel invasion, recurrence rate, and time to recurrence were examined in relation to the immunohistochemical expression of proliferating cell nuclear antigen, sialyl LewisX, and sialyl Lewis(a) in 303 patients with lung cancer who had a curative resection from 1980 to 1991. Of these, 150 had adenocarcinoma, 117 had squamous, 21 had large-cell, and 15 had small-cell carcinoma. Significant differences were detected in the expression of proliferating cell nuclear antigen and sialyl LewisX between adenocarcinomas and the other histologic types; thus the subjects were divided into 150 with adenocarcinoma and 153 with non-adenocarcinoma. In those with adenocarcinoma, the frequency of blood vessel invasion was significantly higher in tumors with strong sialyl LewisX expression, and the disease-free survival of the patients with blood vessel invasion was significantly worse when their tumors strongly expressed both sialyl LewisX and proliferating cell nuclear antigen. In those with non-adenocarcinoma, on the other hand, tumors with strong expression of sialyl Lewis(a) and proliferating cell nuclear antigen showed significantly higher frequencies of blood vessel invasion and worse disease-free survival. In patients with recurrent tumors, those with strong proliferating cell nuclear antigen expression showed a significantly shorter time to recurrence. We conclude that sialyl LewisX and proliferating cell nuclear antigen expression in adenocarcinoma and sialyl Lewis(a) and proliferating cell nuclear antigen expression in non-adenocarcinoma may be an important determinant of recurrence.

Topics: Adenocarcinoma; Antigens, Neoplasm; CA-19-9 Antigen; Carcinoma; Gangliosides; Humans; Lewis X Antigen; Lung Neoplasms; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Nuclear Proteins; Proliferating Cell Nuclear Antigen; Survival Analysis

Topics: ABO Blood-Group System; Adenocarcinoma; Aged; Aged, 80 and over; Antibodies, Neoplasm; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antigens, Neoplasm; Biomarkers, Tumor; Biopsy; Carcinoembryonic Antigen; Diagnosis, Differential; Glycoproteins; Humans; Immunoenzyme Techniques; Lewis X Antigen; Lung Neoplasms; Male; Mesothelioma; Pleural Neoplasms

Fifty primary lung adenocarcinomas were examined immunohistochemically using monoclonal antibodies to determine changes in the expression of N-acetyl-lactosamine (blood group type-2 chain), LeX, LeY and sialyl LeX-i. These antigens were expressed in 60%, 70%, 90% and 94% of carcinomas, respectively; in 8%, 12%, 56% and 86% of normal broncho-bronchiolar epithelium; and in 32%, 0%, 100% and 0% of normal alveolar epithelium. The greater the complexity of the antigenic structure, the greater the incidence of positive staining in the adenocarcinomas. Although the more complex antigens such as sialyl LeX-i and LeY have also been demonstrated in the sera of lung cancer patients, they were not always cancer-selective in our immunohistochemical study. In contrast, the less complex antigens such as N-acetyl-lactosamine (type-2 chain) and LeX seem to be cancer-selective, as they showed low positivity in normal lung tissue.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carbohydrate Sequence; Humans; Immunohistochemistry; Lewis X Antigen; Lung; Lung Neoplasms; Molecular Sequence Data

Topics: Adult; Aged; Antigens, Neoplasm; Antigens, Tumor-Associated, Carbohydrate; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Non-Small-Cell Lung; Female; Humans; Lewis X Antigen; Lung Neoplasms; Male; Middle Aged; Serpins

A 38-year-old man was admitted with persistent productive cough and right anterior chest pain. Chest X-ray showed two large masses connected with each other, one in the right lung field and the other in the anterior mediastinum. A tentative diagnosis of either lung abscess or bronchogenic carcinoma was initially made, because of elevated serum tumor markers (SLX and SCC) and persisting refractory inflammatory sings. However, open chest drainage revealed a few fine hairs and atheromatous materials within the masses, and the diagnosis of teratoma was made. We removed these masses, and investigated the reason for the elevation of tumor markers. Staining with SLX monoclonal antibody demonstrated that the pancreatic tissue in the masses contained SLX. Although this is the first reported case of teratoma producing tumor marker (SLX), it is highly possible that tumor markers may be elevated in the majority of patients with teratoma because of the genesis of this tumor.

Topics: Adult; Carcinoma, Bronchogenic; Diagnosis, Differential; Humans; Lewis X Antigen; Lung Abscess; Lung Neoplasms; Male; Mediastinal Neoplasms; Teratoma

The measurement of serum SLX is thought to be a useful aid in the diagnosis of malignant diseases, particularly adenocarcinoma of the lung. In the present investigation, we measured and compared SLX values in BALF from affected and normal bronchi, obtained from 83 patients. They consisted of 64 males and 19 females, with mean age of 60 years, consisting of 8 normal controls, 19 cases of benign lung disease, and 56 cases of primary lung cancer. SLX value in BALF from normal bronchi was significantly higher in patients with lung cancer than in normal controls, but there was no significant difference in SLX value between lung cancer and benign lung disease. On the other hand, SLX value from affected bronchi was significantly higher in patients with lung cancer than in normal controls and patients with benign lung disease. The rate of elevated SLX in BALF from affected bronchi was significantly higher in patients with lung cancer than in those with benign lung disease. These results suggest that measurement of SLX levels in BALF from affected bronchi may be a useful method for differential diagnosis of primary lung cancer.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Bronchoalveolar Lavage Fluid; Female; Humans; Lewis X Antigen; Lung Diseases; Lung Neoplasms; Male; Middle Aged

Thrombomodulin (TM) is a glycoprotein of molecular weight 75,000 kd that is normally present in restricted numbers of cells, including endothelial and mesothelial cells. In this study, the authors tested the possibility of using anti-TM to facilitate the diagnosis of mesothelioma. All of the 31 mesotheliomas and the two mesothelioma cell lines (MS-1 and MS-2) tested were stained positively with anti-TM. The specificity of anti-TM staining in mesothelioma cells was further confirmed by in situ hybridization of MS-1 cells with a TM-specific probe. The expression of TM in MS-1 cells was increased markedly when these cells were induced by 12-0-tetradecanyl phorbol 13-acetate (TPA) to differentiate. The expression of TM in mesothelioma cells, however, did not correlate with any particular phase of the cell cycle. In an attempt to differentiate pleural mesothelioma from pulmonary adenocarcinoma, the authors compared the expression of TM, carcinoembryonic antigen (CEA), and Leu M1 in these two types of tumors. Only four of 48 (8%) pulmonary adenocarcinomas were stained positively by antibodies to TM. Therefore, immunohistochemical staining with antibodies to TM yielded 100% sensitivity and 92% specificity for diagnosis of mesothelioma. All of the mesotheliomas stained negatively for CEA and Leu M1, except for one, which showed minimal focal positivity for Leu M1. In contrast, 79% and 60% of adenocarcinomas stained positively for CEA and Leu M1, respectively. These findings suggest that immunocytochemical staining with anti-TM should be added to the battery of tests to increase the diagnostic sensitivity and specificity for differentiating mesothelioma from pulmonary adenocarcinoma.

Topics: Adenocarcinoma; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers, Tumor; Carcinoembryonic Antigen; Cell Cycle; Diagnosis, Differential; Humans; In Situ Hybridization; Lewis X Antigen; Lung; Lung Neoplasms; Mesothelioma; Receptors, Cell Surface; Receptors, Thrombin; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured

The serum levels of sialyl stage-specific embryonic antigen (SSEA-1) in 67 patients with adenocarcinoma of the lung were studied to assess their values for diagnosis. A solid-phase immunoradiometric sandwich assay with an FH6 monoclonal antibody was used. Another 49 healthy adults, 52 patients with benign pulmonary diseases, and 142 lung cancer cases with cell types other than adenocarcinoma were evaluated for comparison. The mean (+/- S.D.) levels (U/mL) for adenocarcinoma of the lung, lung cancer other than adenocarcinoma, benign pulmonary diseases and normal subjects were 182.9 +/- 309.7, 53.5 +/- 22.6, 38.9 +/- 17.1 and 30.5 +/- 6.5, respectively. The mean serum sialyl SSEA-1 level was significantly higher in adenocarcinoma of the lung, compared with lung cancer other than adenocarcinoma (p < 0.001), benign pulmonary diseases (p < 0.001), or normal subjects (p < 0.001). For late stage (Stages III and IV, n = 58) adenocarcinoma of the lung, the mean (+/- S.D.) serum sialyl SSEA-1 level (204.3 +/- 327.6 U/mL) was significantly higher than that of earlier stage (Stages I and II, n = 9) adenocarcinoma of the lung (39.9 +/- 19.3), p < 0.001. There was no statistical difference among the mean serum levels of various histologic types of lung cancer other than adenocarcinoma (p > 0.05). In the lower range of values, considerable overlap existed between adenocarcinoma of the lung and lung cancer other than adenocarcinoma. However, very high sialyl SSEA-1 levels (> 140 U/mL) were only encountered in late stage adenocarcinoma of the lung (22/58).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Adult; Aged; Female; Humans; Lewis X Antigen; Lung Neoplasms; Male; Middle Aged

Progressive growth of metastatic Lewis lung carcinoma (LLC) tumors results in a concurrent stimulation of myelopoiesis and the appearance of immune-suppressive bone marrow cells. The present study has shown that normal bone marrow cells could be induced to become immune-suppressive by 3 days of culture with supernatants of cloned metastatic LLC-LN7 variant cells. The capacity of the LLC-LN7 supernatants to stimulate the appearance of suppressor cells was directly proportional to the concentration of supernatant used in the bone marrow culture. When adoptively transferred with a LLC-LN7 tumor inoculum, the supernatant-induced suppressor bone marrow cells increased the rate of appearance of palpable tumors and the frequency of tumor establishment. The LLC-LN7 supernatants containing suppressor-cell-inducing activity also had colony-stimulating factor (CSF) activity. The CSF activity produced by the LLC-LN7 cells could be diminished with neutralizing antibodies to either granulocyte/monocyte(GM-) CSF or to interleukin-3 (IL-3). Likewise, the suppressor-inducing activity in the LLC-LN7 supernatants was diminished by pretreatment with anti-GM-CSF or anti-IL-3. The combination of anti-GM-CSF and anti-IL-3 completely neutralized all suppressor-inducing activity produced by the LLC-LN7 cells. These results suggest that the secretion of IL-3 and GM-CSF by LLC-LN7 tumor cells is a mechanism by which the tumors stimulate myelopoiesis and induce normal bone marrow cells to become immune-suppressive. Bone marrow cells that are induced to become immune-suppressive by culture with LLC-LN7 supernatants can, in turn, facilitate the establishment of tumor in vivo.

Topics: Animals; Bone Marrow; Colony-Stimulating Factors; Concanavalin A; Dose-Response Relationship, Drug; Immune Tolerance; In Vitro Techniques; Lewis X Antigen; Lung Neoplasms; Male; Mice; Mice, Inbred C57BL; T-Lymphocytes, Regulatory; Tumor Cells, Cultured

One hundred and five cases of various human lung neoplasms were studied immunohistochemically using monoclonal antibodies recognizing the antigens, Le(x), sialylated Le(x) (SLEX), Le(a), and sialylated Le(a) (SLEA). Of the 92 lung cancers examined for antigen expression SLEX was detected in 57% (52 cases), Le(x) in 42% (39), SLEA in 36% (33), and Le(a) in 23% (21). None of these antigens were expressed in 9 tumor like lesions of the lung or the 4 other non-epithelial malignant lung tumors examined. Higher expression was seen in the 54 lung adenocarcinomas: SLEX in 72%, Le(x) in 48%, SLEA in 39%, and Le(a) in 24%. The type 2 carbohydrate antigens (SLEX and Le(x) were more prevalent than the type 1 antigens (SLEA and Le(a)) in lung adenocarcinoma tissues. In adenocarcinomas, SLEX was expressed in 71% (10/14) of the Le(b) patients, and in 100% (5/5) of the Le(a) patients. Unexpectedly, SLEX was not detected in 4 out of 5 Le(a-b-) patients tested. This suggests that the expression of the Le(x) antigens and the Le(a) antigens are related in lung adenocarcinoma. These antigens were less expressed in other types of lung cancers. Tissue sections obtained serially showed heterogeneity in the expression of these antigens, as evidenced by the concurrent presence of both SLEX and SLEA. These results indicate that SLEX is a useful tumor-associated marker for lung adenocarcinomas, and that terminal fucosylation and sialylation may be activated heterogeneously in these lung cancers.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antigens, Neoplasm; Biomarkers, Tumor; Blood Group Antigens; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Cell Differentiation; Gene Expression Regulation, Neoplastic; Glycosylation; Humans; Lewis Blood Group Antigens; Lewis X Antigen; Lung Neoplasms; N-Acetylneuraminic Acid; Sialic Acids

Serum levels of CA-50, SLX and ST-439 were measured in 213 patients with lung cancer (92 adenocarcinomas, 63 squamous cell carcinomas, 37 small cell carcinomas and 21 large cell carcinomas) and 87 patients with benign lung disease. The overall positive rates in patients with lung cancer were 12.8% for CA-50, 29.7% for SLX and 25.3% for ST-439. The positive rates for CA-50, SLX and ST-439 in adenocarcinoma patients were 22.8%, 42.4% and 38.0%, respectively. Of the patients with benign lung disease, 4.8% were false positive for CA-50, 15.3% for SLX and 3.6% for ST-439. In the patients with adenocarcinoma of the lung, the combination assay of CEA and ST-439 had a highly accurate rate (61.9%).

Topics: Adenocarcinoma; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Humans; Lewis X Antigen; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging

Serum SLX, CEA, SCC and NSE levels were serially measured in 266 patients with lung cancer and compared with those in 345 patients with benign respiratory disorders (BRD). The positive rate for CEA in lung cancer (44.4%) and the false-positive rate in BRD (15.3%) were the highest among the 4 markers. The positive rate for SLX in lung cancer (32.0%) was lower than that of CEA, while the false-positive rate for SLX in BRD (7.2%) was lower than that of CEA. The positive rate for SLX was highest in adenocarcinoma and correlated better with the clinical stages than did CEA. SCC and NSE were specifically elevated in squamous cell carcinoma and small cell carcinoma, respectively. Using these 4 markers, only 70.2% of patients were correctly diagnosed as having lung cancer or BRD. In monitoring treatment effect, only SLX showed a statistically significant correlation with regression and progression in adenocarcinoma, while NSE and SLX showed such a correlation in small cell carcinoma. Serum tumor markers seem to be less sensitive for the diagnosis of lung cancer than chest X-ray and sputum cytology, indicating that a search for more specific markers is still required. However, in monitoring treatment effect, SLX appeared to be suitable for adenocarcinoma, while NSE and SLX seemed to be useful in small cell carcinoma.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Humans; Lewis X Antigen; Lung Neoplasms; Male; Middle Aged; Phosphopyruvate Hydratase; Serpins

The clinical significance of tumor-associated glycosylated antigen, sialylated Lewisx (SLEX) was demonstrated with reference to pulmonary diseases by fluorescent enzyme immunoassay. In benign lung diseases 5.5% were positive for serum SLEX. Lung cancer, the highest percentage positivity was seen in adenocarcinoma (41.7%), and clinical stage III and IV showed 36.2% and 41.9%, respectively. These results indicate that SLEX might conceivably be useful as a tumor marker, particularly for adenocarcinoma of the lung. Using Sephacryl S-1000 columns the elution profiles of sera and bronchoalveolar lavage in cases of lung cancer, gastric cancer and diffuse panbronchiolitis were also investigated, and it was concluded that the release mechanism of the antigen into blood stream in the malignant diseases is different from that in benign disease and the carrier protein binding to the antigen varies according to the disease.

Topics: Adenocarcinoma; Adult; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Humans; Immunoenzyme Techniques; Lewis X Antigen; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging

Topics: Biomarkers, Tumor; Female; Glycolipids; Humans; Immunoradiometric Assay; Lewis X Antigen; Lung Neoplasms; Male; Ovarian Neoplasms; Pancreatic Neoplasms; Specimen Handling

The localization of two carbohydrate antigens, I and sialyl I antigens, in the lungs of developing human embryos was investigated using specific monoclonal antibodies and compared with the distribution patterns of the known embryonic antigen, stage-specific embryonic antigen-1 (Lex hapten). When the future bronchi were actively developing from the bronchial buds in the lungs of 50- to 53-day-old embryos, the immature bronchial bud cells were I-, Lex+, while the fully differentiated epithelial cells of the larger bronchus were I+, Lex-. When the bronchiolar bud cells matured into bronchiolar epithelial cells in the lung of a 12-week-old embryo, the immature bronchiolar bud cells were I-,Lex+, while the fully differentiated epithelial cells of the bronchioles were I+,Lex-. Sialylated forms of the antigens finally appeared in the lungs of 18-week-old embryos, when the terminal bud cells actively proliferated and underwent the differentiation process into epithelial cells of alveoli and alveolar ducts. The immature terminal bud cells at this stage were I-, sialyl I-, Lex+, sialyl Lex-i+, while the fully differentiated alveolar epithelial cells were I+, sialyl I+, Lex-, sialyl Lex-i-. After 8 months, the flattened mature alveolar epithelial cells were strongly positive for both I and sialyl I antigens, the strong expression of which continued after birth and even into the adult stage. These distribution patterns indicate that the I and sialyl I antigens are specific markers for the differentiated type cells in each stage of development, while Lex and related embryonic antigens were specific to the immature bud cells in every stage. The above-described differentiation-dependent expression patterns of these antigens seem to be reflected in the distribution of these antigens in human lung cancers, i.e., I and sialyl I antigens were expressed in lung cancer cells more weakly than in normal lung cells, while the Lex and sialyl Lex-i were expressed in cancer cells much more strongly than in normal lung cells. This was further reflected in the serum levels of these antigens in the patients with respiratory disorders. The distribution pattern of the serum levels of these antigens in patients with lung cancers showed sialyl Lex-i greater than sialyl I, indicating that these serum antigens originated from the lung cancer lesion where sialyl Lex-i is much more dominant than sialyl I antigen.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adenocarcinoma; Antibodies, Monoclonal; Embryo, Mammalian; Embryonic and Fetal Development; Gene Expression; Histocompatibility Antigens Class II; Humans; Immunohistochemistry; Lewis X Antigen; Lung; Lung Neoplasms

Sialyl stage-specific mouse embryonic antigen (SSEA-1) levels were measured in pleural effusions obtained from patients with lung cancer and benign pulmonary disease, using a solid-phase immunoradiometric sandwich assay. The mean (+/- SEM) levels (unit/ml) of pleural fluid sialyl SSEA-1 were 3620 +/- 1419 in adenocarcinoma (n = 25), 123 +/- 30 in nonadenocarcinoma (n = 13) and 95 +/- 19 in benign pulmonary disease (n = 13), respectively. The positive rate was 64% in adenocarcinoma, 7.7% in nonadenocarcinoma, and 0% in benign pulmonary disease, respectively, when a cutoff level was defined as the mean + 3 SD value (300 unit/ml) based on pleural fluid sialyl SSEA-1 levels in benign pulmonary disease. There was a significant positive correlation between pleural fluid levels of sialyl SSEA-1 and those of carcinoembryonic antigen in adenocarcinoma patients (r = 0.8246, P less than 0.01). Pleural fluid sialyl SSEA-1 levels correlated with cytologic findings in adenocarcinoma patients. These observations suggest that sialyl SSEA-1 in pleural effusion is a useful marker to discriminate malignant from nonmalignant and adenocarcinoma from nonadenocarcinoma of the lung.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Carcinoembryonic Antigen; Female; Glycolipids; Humans; Lewis X Antigen; Lung Neoplasms; Male; Middle Aged; Pleural Effusion; Radioimmunoassay

Stage-specific embryonic antigen-1 (SLX) is a glycolipid recognized by a monoclonal antibody (FH 6) which is produced by cells immunized with mice teratocarcinoma cell line. Using an SLX (Otsuka) kit from Ostuka Assay Laboratory, we measured the serum level of SLX in 96 patients with lung cancer, 305 patients with non-cancerous lung disease and 86 healthy adults, prospectively. When we adopted a cutoff level of 42U/ml (mean + 2S.D. in the healthy adults), the overall positive rates were 29.2% in the lung cancer patients, 15.1% in the non-cancerous patients and 0% in the healthy adults. The positive rate of the lung cancer patients was significantly higher than in the patients with non-cancerous lung disease (p less than 0.05). According to the histological type of lung cancer, the positive rates were 40.9% in 44 patients with adenocarcinoma, 18.4% in 37 patients with squamous cell carcinoma, 0% in 7 patients with small cell carcinoma, and 0% in 3 patients with large cell carcinoma. Staging of the lung cancer patients revealed positive rates for serum SLX of 5.6% in 18 stage I patients, 22.2% in 9 stage II patients, 33.3% in 21 stage IIIA patients, 33.3% in 27 stage IIIB patients, 42.9% in 21 stage IV patients. After we performed the immunostaining method for SLX using FH6, positive immunoactivity was demonstrated mainly in the cell membrane of adenocarcinoma cells. SLX seems to be a tumor-associated marker in patients with lung adenocarcinoma.

Topics: Adenocarcinoma; Adult; Biomarkers, Tumor; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Glycolipids; Humans; Lewis X Antigen; Lung Neoplasms; Reference Values

CA130 is a glycoprotein which is recognized by monoclonal antibodies-(130-22 and 145-9) produced by immunization with human lung adenocarcinoma cell line (PC-9). CA130 is considered to be a new tumor marker, different from CA125, since it has a separate antigenic determinant. We used the D-7111 kit (Daiichi Radioisotope Laboratories, Ltd.) to measure the serum level of CA130 in 290 patients with lung cancer, 171 patients with noncancerous lung disease (N-CLD) and 93 healthy adults. In addition, CEA, CA19-9, CA125 and sialyl SSEA-1 antigen (SLX) were also measured for the same serum samples when possible. The cutoff level for CA130 was 35 U/ml. The overall positive rates for CA130 were 32% in the lung cancer patients, 23% in the N-CLD patients and 0% in the healthy adults. The positive rate in the lung cancer patients was significantly higher than in the N-CLD patients (p less than 0.05). As a function of the histological type of lung cancer, the positive rates for CA130 were 44% in 120 patients with adenocarcinoma, 17% in 115 patients with squamous cell carcinoma, 33% in 36 patients with small cell carcinoma, 42% in 12 patients with large cell carcinoma and 29% in 7 patients with miscellaneous cell type. The positive rate in the patients with adenocarcinoma was significantly higher than in the patients with squamous cell carcinoma (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma; Glycolipids; Humans; Lewis X Antigen; Lung Neoplasms

Serum levels of sialylated Lewisx (SLEX) and sialylated SSEA-1 (S-Xi) in 136 cases of diagnosed lung cancer (63 adenocarcinoma, 45 squamous cell carcinoma, 20 small cell carcinoma and 8 large cell carcinoma) and 111 cases of benign pulmonary disease were measured. The positive rate of these markers in the primary lung cancer group was significantly higher than those in benign pulmonary diseases. The positive rates of serum SLEX and S-Xi in all lung cancer cases were 27.2% and 27.9%, respectively. The antigen levels in the sera were higher in adenocarcinoma as compared to other histologic types, and increased as the stage advanced. It was concluded that SLEX and S-Xi are very useful markers of lung cancer for diagnosis and monitoring the clinical status.

Topics: Adenocarcinoma; Biomarkers, Tumor; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Gangliosides; Glycolipids; Humans; Lewis X Antigen; Lung Neoplasms

Tumor tissues obtained from 5 cases of malignant mesothelioma and from 5 cases of primary adenocarcinoma of the lung have been studied on staining with the sialyl SSEA-1 antibody by the PAP method. Results in all cases of a malignant mesothelioma (both Epithelioid and Sarcomatous pattern) were absolutely negative. All cases of lung cancer, however, were positive, though in differing degrees. In evaluating a malignant mesothelioma, many reports have indicated that the negativity of CEA staining is useful in achieving the differential diagnosis from lung cancer. The sensitivity of the staining by sialyl SSEA-1 was found to be far better than that of CEA in examining either malignant mesothelioma or lung cancer. Thus, we found that not only CEA but also sialyl SSEA-1 antigen staining was useful for the diagnosing of a malignant mesothelioma.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antigens, Neoplasm; Carcinoembryonic Antigen; Diagnosis, Differential; Female; Glycolipids; Humans; Lewis X Antigen; Lung Neoplasms; Male; Mesothelioma; Staining and Labeling

Enzyme conjugates with antibody of IgG type have been used extensively in immunohistochemistry, but conjugates with antibody of IgM type have not been reported. This paper describes the beta-D-galactosidase (Gal) labeling of a monoclonal IgM antibody designated CSLEX1 (for cytotoxic sialosylated Lewisx), which is directed against a tumor-associated antigen sialosylated Lewisx (S-Lex). The antibody was first acylated with a heterobifunctional agent N-(gamma-maleimidobutyryloxy)succinimide (GMBS) to introduce the maleimide groups into the molecule; excess reagent was removed by gel filtration and then the activated antibodies were crosslinked to the thiol groups of Gal. The conjugates were partially purified of free Gal by DEAE-Toyopearl column chromatography with an increasing linear concentration of NaCl. The conjugates thus prepared retained almost full enzyme activity and were demonstrated to be free of CSLEX1 by affinity chromatography using anti-galactosidase antibody bound to Sepharose 4B. The conjugates were used as a label in a sandwich enzyme immunoassay (SEIA) to detect the antigen at concentrations as low as 0.2 U/well. The SEIA was used to measure serum S-Lex levels in both healthy subjects and lung cancer patients and mean concentrations of 70 U/ml and 198.6 U/ml were detected respectively.

Topics: Animals; Antibodies, Monoclonal; Antigen-Antibody Reactions; Antigens, Neoplasm; beta-Galactosidase; Dose-Response Relationship, Immunologic; Enzyme Stability; Galactosidases; Gangliosides; Humans; Immunoenzyme Techniques; Immunoglobulin M; Lewis X Antigen; Lung Neoplasms; Mice; Oligosaccharides; Succinimides

Tumor markers including sialyl SSEA-1 antigen (SLX) were measured in 77 patients with lung cancer and 116 patients with benign respiratory diseases. Increased levels of serum SLX were observed in 57.6% (19/33) of adenocarcinoma of the lung, and an overall positive rate was 42.9% (33/77) in lung cancer cases. The false positive incidence of SLX in the sera from the patients with non-malignant diseases was as low as 8.6%. Among other tumor markers determined, serum CA 19-9, CEA had a relatively high positive rate, but the false positive incidence were not low. In cases of poor prognostic cases of with adenocarcinoma of the lung, SLX levels became levels higher than the previous ones, but not in cases of other cell types were not. Not only in the patients with lung cancer but also in those with benign respiratory diseases such as bronchiectasis and lung fibrosis, high levels of SLX seemed to suggest poor prognosis. These results indicate that SLX may contribute for monitoring and prognosis of the cases of lung cancer and other respiratory diseases.

Topics: Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Carcinoembryonic Antigen; Glycolipids; Humans; Lewis X Antigen; Lung Diseases; Lung Neoplasms; Prognosis

The localization of three carbohydrate antigens, Lex, Ley, and sialylated Lex-i, which are closely related to stage-specific embryonic antigen 1, in the lung of developing human embryos was investigated using specific monoclonal antibodies. In the 38-day-old embryo, when the primitive lung bud has appeared and developed into two lung sacs, only Ley antigen was specifically positive in the proliferating cells in the terminal portion of lung bud. In the 50-53-day-old embryos, the future bronchi were actively developing from the bronchial buds. At this stage, the Ley antigen was maximally expressed and the Lex antigen appeared in the bud cells. In the lung of the 12-week-old embryo, buds for the future bronchioles were lined by simple cuboidal epithelial cells, which were strongly positive for Lex antigen, weakly positive for Ley antigen, and still completely negative for sialylated Lex-i antigen. Sialylated Lex-i antigen finally appeared in 18-week-old embryos, in the cells of the terminal buds for the future alveoli. At this stage, the Lex and Ley antigens were already beginning to disappear and were only weakly positive in cells of terminal buds. At 20 weeks, only sialylated Lex-i antigen was weakly detected in the cells in the terminal buds; after 8 months, all three antigens were essentially not detected in the respiratory cells in most of the embryos examined in this study. Formation of bronchial glands was detected at 18 weeks, where the developing gland cells were specifically positive for sialylated Lex-i antigen. Ciliation of the bronchial epithelial cells started at 12 weeks and propagated thereafter. The ciliation was accompanied by the reappearance of Ley and Lex antigen in the epithelial cells. These findings collectively indicated that the three antigens all have a physiological significance as stage-specific developmental antigens of the human lung; those antigens were specifically present in the bud cells at each important step of the morphogenesis of the human lung, such as cells in the lung buds, bronchial buds, and terminal buds for the formation of the alveolus, and cells differentiating into bronchial gland cells. The three antigens gradually disappear in the later stage of development along with the maturation process of the lung. Stage-specific embryonic antigen 1 and related antigens are known to be associated with various human cancers, including lung cancers. We suggest that the expression of these antigens in the lung cancer cells

Topics: Adenocarcinoma; Antibodies, Monoclonal; Glycolipids; Humans; Lewis Blood Group Antigens; Lewis X Antigen; Lung; Lung Neoplasms

The properties of the antigen recognized by monoclonal antibody FH6 have been analyzed. FH6 was originally generated against a glycolipid, i.e. a difucoganglioside isolated from human colonic adenocarcinoma, and specifically reacts with sialyl Lex-i determinant. Several culture supernatants of human carcinoma cell line cells were found to have high levels of FH6-reactive antigen, and PC-9, a human lung carcinoma cell line was used for the analysis. A solid-phase sandwich radioimmunoassay was performed to detect the antigen. The antigenic activity was extractable in 0.6 M PCA or 7% TCA, and was sensitive to mild alkaline treatment and to Pronase digestion. Most of the antigen was eluted in the void volume of a Sepharose CL-2B column, which indicates that its molecular weight is greater than several million. It was eluted from a DEAE-cellulose column at a NaCl concentration in the range of 0.2-0.25 M. The immunoaffinity-purified antigen has a high carbohydrate content of more than 80%. These data indicate that the antigen recognized by FH6 in the culture supernatant of PC-9 is not a glycolipid, but a high molecular weight glycoprotein which could be referred to as a mucin, or a proteoglycan, which contains keratan-sulfate like glycosaminoglycan chains, as judged from the results of the glycosidase treatments.

Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Carbohydrate Sequence; Chromatography, Affinity; Chromatography, Gel; Chromatography, Ion Exchange; Culture Media; Glycolipids; Glycoproteins; Glycoside Hydrolases; Humans; Lewis X Antigen; Lung Neoplasms; Molecular Sequence Data; Tumor Cells, Cultured

The clinical significance of serum sialyl SSEA-1 antigen was evaluated using the sera of 1261 patients with malignant tumors and 717 patients with non-malignant diseases measured with Otsuka Assay Laboratories' RIA Kits. The results indicate that the antigen was frequently elevated in the sera from the patients with various adenocarcinomas, including lung (45%), pancreas (64%) and ovary (57%). The false positive incidence of antigens in the sera from the patients with non-malignant disorders was as low as 4.9%. No correlation was observed with other tumor markers examined in this study, and the diagnostic efficiency increased significantly by the combined determination of sialyl SSEA-1 antigen level with other markers. The serial determination of the serum sialyl SSEA-1 antigen level has a clinical utility also in monitoring the patients with adenocarcinoma receiving surgical operation and/or chemotherapy as indicated by the results of the longitudinal observation of the patients.

Topics: Adenocarcinoma; Antigens, Neoplasm; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Evaluation Studies as Topic; Female; Gastrointestinal Neoplasms; Glycolipids; Humans; Lewis X Antigen; Lung Diseases; Lung Neoplasms; Male; Radioimmunoassay; Reagent Kits, Diagnostic

The mouse embryonal carcinoma cell line F9 differentiates into parietal endoderm cells after a 3-day exposure to retinoic acid and dibutyryl cyclic AMP. Using the experimental metastases assay, we investigated the organ colonization properties of RA-treated and -untreated populations of F9 cells. The results show that untreated F9 cells colonize the liver with a high degree of specificity while the treated populations colonize the lungs. Cells derived from a lung colony colonized only the liver unless they were treated with RA. However, removal of the inducer from culture of differentiated cells did not cause reversal of the lung colonization potential. Our observations also indicate that it is unlikely that lung colonization is due to cell aggregation or to interaction between differentiated and undifferentiated cells. Taken together, these results suggest that RA induces the observed changes of organ colonization properties of F9 cells.

Topics: Animals; Bucladesine; Cell Line; Fucose; Glycolipids; Glycosylation; Lewis X Antigen; Liver Neoplasms; Lung Neoplasms; Mice; Neoplasm Metastasis; Teratoma; Tretinoin

Bronchopulmonary carcinomas were analyzed immunohistochemically using monoclonal antibody 624A12. The antibody was raised against a human "small cell carcinoma" cell line NCI-H69. It recognizes a particular sugar sequence in lacto-N-fucopentose III, which is preserved in formalin fixed and paraffin embedded tissue. Various bronchopulmonary carcinomas revealed characteristic patterns of immunoreactivity. Forty nine/50 adenocarcinomas were immunoreactive either diffusely or focally. The immunostaining was usually limited to the cell membranes with occasional intracytoplasmic immunostaining in large cells. The only negative case had been irradiated before surgical resection. Twenty seven/38 squamous cells carcinomas did not immunostain while the remaining 11 displayed focal immunoreactivity in areas of "loose cellular apposition" associated with necrosis and, rarely, in squamous pearls. All of six adenosquamous carcinomas showed immunoreactivity focally. Eleven/30 large cell carcinomas and 10/11 bronchiolo-alveolar carcinomas were either diffusely or focally immunoreactive. Seven/26 intermediate cell neuroendocrine carcinomas were focally immunoreactive while none of 33 typical small cell neuroendocrine carcinomas, 21 carcinoids, and 10 well differentiated neuroendocrine carcinomas was immunoreactive. An adenoid cystic carcinoma was diffusely immunoreactive, and a mucoepidermoid carcinoma was focally immunoreactive. We conclude that various bronchopulmonary neoplasms have characteristic patterns of distribution of this antigen, and that monoclonal antibody 624A12 may be useful for the differential diagnose among bronchopulmonary carcinomas, and their differential diagnosis from pleural mesotheliomas.

Topics: Adenocarcinoma; Adenocarcinoma, Bronchiolo-Alveolar; Animals; Antibodies, Monoclonal; Carcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Line; Humans; Lewis X Antigen; Lung Neoplasms; Mice; Mice, Nude; Oligosaccharides

SSEA-1 antigen (stage-specific embryonic antigen-1) has been shown to be a series of carbohydrate antigens having type-2 chain and X-hapten structures. These carbohydrate antigens are remarkably accumulated in various human cancer tissues, and activity secreted into the blood stream. Frequently SSEA-1 antigens are further modified with fucoses or sialic acid in human cancer tissues, thus forming various subgroups of antigens such as fucosyl SSEA-1, sialyl SSEA-1 or polyfucosylated antigens. Many monoclonal antibodies are established which can discriminate each subgroup of antigens. Assay systems for these antigens in the sera of cancer patients have been developed using these monoclonal antibodies. Sialyl SSEA-1 is especially elevated in the sera of patients with adenocarcinoma of the lung. The antigens detected with these monoclonal antibodies are mucin-like glycoproteins(cancer-associated mucin, CAM). Various types of cancer-associated mucins can be characterized by respective monoclonal antibodies. It is therefore possible to classify cancer-associated mucins according to the structure of their carbohydrate side chains using these monoclonal antibodies.

Topics: Adenocarcinoma; Animals; Antibodies, Monoclonal; Antigens, Neoplasm; Carbohydrates; Colonic Neoplasms; Glycolipids; Humans; Lewis X Antigen; Lung Neoplasms; Mice; Mucins; Stomach Neoplasms

Monoclonal antibodies made against gastrointestinal carcinoma antigen (GICA) and stage specific embryonic antigen (SSEA) were evaluated for their ability to distinguish normal mesothelial cells present in pleural and peritoneal fluids from adenocarcinoma cells in tissue and cytology specimens. The presence of GICA was documented in a high percentage of adenocarcinomas from the gastrointestinal tract (75/98) and in 52% of pulmonary (15/29) and 29% of ovarian (6/21) adenocarcinomas. GICA was found infrequently in breast carcinoma (1/18) and not in mesotheliomas (0/16). A similar pattern of GICA expression was seen in malignant effusions from adenocarcinomas (18/47) and mesotheliomas (0/6). SSEA was found in a high percentage of adenocarcinomas derived from the gastrointestinal tract (47/56) and the lung (26/29). SSEA was detected in breast carcinoma (8/15) more often than GICA. SSEA was detected rarely in mesotheliomas (1/16). Reactivities for epithelial membrane antigen, keratin, carcinoembryonic antigen, GICA and SSEA in adenocarcinoma and mesotheliomas were compared.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antigens, Neoplasm; Antigens, Surface; Antigens, Tumor-Associated, Carbohydrate; Breast Neoplasms; Diagnosis, Differential; Female; Gastrointestinal Neoplasms; Glycolipids; Humans; Lewis X Antigen; Lung Neoplasms; Mesothelioma; Ovarian Neoplasms

The distribution in paraffin fixed human tissues of a carbohydrate antigen defined by two monoclonal antibodies raised against human granulocytes has been studied by means of an immunoperoxidase technique. In addition to granulocytes, the antigen has been detected in adult tissues on identifiable cell types of the stomach, kidney, adrenal medulla, and brain and on the mucins of the gastrointestinal tract and other secretions. In fetal tissue, epithelial cells of the alimentary tract, lung, brain, and kidney express the antigen. Adenocarcinoma of the colon, stomach, breast, and lung are stained strongly, as are other types of lung cancer. The monoclonal antibodies give a staining pattern similar but not identical to other monoclonal antibodies raised against granulocytes or neoplastic cell lines which recognise the antigen 3-fucosyl N-acetyllactosamine. The use of antibodies against this oncofetal antigen in the study of differentiation and as tumour markers is discussed.

Topics: Adrenal Medulla; Animals; Antibodies, Monoclonal; Antigens; Antigens, Neoplasm; Brain; Colonic Neoplasms; Digestive System; Epitopes; Fetus; Granulocytes; Humans; Immunoenzyme Techniques; Kidney; Lewis X Antigen; Lung Neoplasms; Mice; Mice, Inbred BALB C; Oligosaccharides

Topics: Antibodies, Monoclonal; Antibodies, Neoplasm; Antibody Specificity; Carbohydrate Sequence; Cerebrosides; Humans; Lewis X Antigen; Lung Neoplasms; Oligosaccharides