Cardiac troponin I for predicting right ventricular dysfunction and intermediate risk in patients with normotensive pulmonary embolism.

BACKGROUND: Right ventricular dysfunction (RVD) and cardiac troponin I (cTnI) are important tools for risk stratification in pulmonary embolism (PE). We investigate the association of RVD and cTnI in normotensive PE patients and calculate a cTnI cut-off level for predicting RVD and submassive PE. METHODS: Clinical, laboratory, radiological and echocardiagraphic data were analysed. Patients were categorised into groups with or without RVD and compared focussing on cTnI. Effectiveness of cTnI for predicting RVD and submassive PE was tested. RESULTS: One hundred twenty-nine normotensive PE patients, 71 with and 58 without RVD, were included. Patients with RVD were older (75.0 years (61.3/81.0) vs. 66.0 years (57.7/75.1), P = 0.019). cTnI (0.06 ng/ml (0.02/0.23) vs. 0.01 ng/ml (0.00/0.03), P < 0.0001) and D-dimer values (2.00 mg/l (1.08/4.05) vs. 1.23 mg/l (0.76/2.26), P = 0.016) were higher in PE with RVD. cTnI was associated with RVD (OR 3.95; 95 % CI 1.95-8.02, p = 0.00014). AUC for cTnI diagnosing RVD was 0.79, and for submassive PE0.87. Cut-off values for cTnI predicting RVD and submassive PE were 0.01 ng/ml, with a negative predictive value of 73 %. cTnI was positively correlated with age, D-dimer and creatinine. CONCLUSIONS: In normotensive PE patients, cTnI is helpful for risk stratification and excluding RVD. cTnI elevation is correlated with increasing age and reduced kidney function.

Microsatellite instability and Beta2-Microglobulin mutations as prognostic markers in colon cancer: results of the FOGT-4 trial.

BACKGROUND: High-level microsatellite instability (MSI-H) has been reported as a prognostic marker in colon cancer. We here analysed the prognostic significance of MSI and mutations of the Beta2-Microglobulin (B2M) gene, which occur in about 30% of MSI-H colon cancer, in the cohort of the prospective FOGT-4 (Forschungsruppe Onkologie Gastrointestinale Tumoren, FOGT) trial. METHODS: Microsatellite instability status was determined using standard protocols (NCI/ICG-HNPCC panel and CAT25) in 223 colon cancer lesions. Beta2-Microglobulin mutation status was evaluated by exon-wise sequencing in all MSI-H lesions. RESULTS: Patients with MSI-H (n=34) colon cancer presented with a significantly lower risk of relapse after 12 months of follow-up compared with MSS (n=189) colon cancer patients (5 year time to relapse: MSI-H 0.82 vs MSS 0.66, P=0.03). No significant difference in overall survival was detected. Beta2-Microglobulin mutations were identified in 10 (29.4%) out of 34 MSI-H colon cancers and were associated with a complete absence of disease relapse or tumour-related death events (P=0.09). CONCLUSION: The risk of late disease relapse was significantly lower in patients with MSI-H compared with MSS colon cancer. Moreover, B2M mutations may contribute to the favourable outcome of MSI-H colon cancer patients and should therefore be evaluated as a potential prognostic marker in future clinical trials.

[Cyclic vomiting syndrome (CVS) in adults - frequently overlooked?]. / Zyklisches Erbrechenssyndrom (CVS) beim Erwachsenen - eine häufig übersehene Erkrankung?

CVS (cyclic vomiting syndrome) is a functional disorder that can occur in all age groups. Adults typically develop CVS in middle age (around the 35th year of life). CVS is characterised by recurrent stereotypic episodes of nausea and vomiting lasting hours or some days. Between these episodes there are intervals free of symptoms. The main symptoms include nausea, vomiting and often abdominal pain. CVS is a rare disorder in adult patients. Because of the lack of awarness, making the correct diagnosis is not easy und often delayed for some months or years. There is no specific test to secure the diagnosis. The accurate diagnosis is based on the typical anamnestic report and the exclusion of other disorders associated with a recurrent vomiting. No standard evidence-based treatment is currently available either to manage the acute vomiting episode or to manage the prophylactic therapy. For the acute treatment of the vomiting episodes antiemetic, antimigraine and sedative medications were used. The medications frequently used for the prophylactic therapy are amitriptyline and propranolol.

[Stereotypical episodes of vomiting for 11 years in a 33-year-old patient]. / 33-jähriger Patient mit stereotypen Erbrechensepisoden seit 11 Jahren.

A 33-year-old man was admitted because of severe vomiting. For the last 11 years, he had suffered recurrent stereotypical episodes of vomiting lasting 3-4 days. The episodes of vomiting occurred 10-15 times a year. Moreover his brother and his mother had similar symptoms. Thus, (familial) cyclic vomiting syndrome was diagnosed. With the help of antiemetic and sedative drugs, the acute vomiting episode was stopped. Prophylactic therapy with amitriptyline was started, which led to a symptom-free period of 3.5 years without a new episode of vomiting.

GD3, a prominent ganglioside of human melanoma. Detection and characterisation by mouse monoclonal antibody.

Mouse monoclonal antibody AbR24 has a high degree of specificity for human melanoma cells when tested on viable cultured cells using the protein A mixed hemagglutinin serological assay. The antigen detected by this antibody has been isolated from melanoma cells and shown to be GD3 ganglioside by compositional and partial structural analysis and by comparison with authentic GD3 in thin layer chromatography (TLC). AbR24 reacts with authentic GD3, but not with any other ganglioside tested. Using TLC and reactivity with AbR24, a wide range of cells and tissues was examined for the presence of GD3. A new serological assay, termed glycolipid-mediated immune adherence, was devised for assaying the reactivity of AbR24 with gangliosides. Melanomas (cultured cells or tumor tissue) were shown to have GD3 and GM3 as major gangliosides. Other cells and tissues examined also contained GD3, but usually only in low amounts. Melanomas (and MOLT-4, a T cell line) were characterized by a simplified ganglioside profile with GD3 and GM3 as major components. The apparent discrepancy between the ubiquitous presence of GD3 and the serological specificity of AbR24 for melanoma cells can be explained in terms of localization and concentration of GD3 in different cells.

Modes of binding and internalization of monoclonal antibodies to human melanoma cell lines.

The process of monoclonal antibody (MAb) binding to tumor cells is greatly influenced by the biology of the respective antigen. This was concluded from an analysis of binding and release of MAbs and MAb fragments to melanoma cells at different concentration levels and different temperatures. With an antigen known to be stably expressed at the cell surface (i.e., Mr 97,000 protein) rapid binding of MAbs was observed at both 0 degrees C and 37 degrees C, and this was reversed by treatment with isoosmolar acid buffer. With another group of antigens, MAb binding increased continuously up to considerable levels at 37 degrees C, but not at 0 degrees C. Concomitantly, the portion of radioactive MAb not desorbable by acid buffer treatment increased, pointing to temperature-dependent internalization. With still another group of (glycolipid) antigens, the highest MAb binding was obtained with fixed cells at 0 degrees C. In this situation MAb release was particularly rapid, thus pointing to a shedding process.

Inhibition of human melanoma cell growth in vitro by monoclonal anti-GD3-ganglioside antibody.

Malignant melanoma cell growth in vitro was blocked by the monoclonal antibody R-24, which detects the disialoganglioside GD3 on melanoma cells. GD3 expression varies greatly in cultured human malignant melanoma cells. The level of ganglioside GD3 was measured by quantitative absorption tests. In our observations, six melanoma cell lines expressing high levels of GD3 on the cell surface showed growth inhibition and rounding up in the presence of R-24 antibody. Four melanoma cell lines with low levels of GD3 and seven nonmelanoma cell lines with no detectable GD3 remained unchanged in morphology and continued to grow. The data presented indicate that complement is not involved in the growth inhibition observed here. Because ganglioside GD3 was detected in all 16 tissue specimens of primary and metastatic human malignant melanoma examined by immunofluorescence tests, the possible relevance of this finding in vivo is discussed.

Secretory epithelial cell marker on gastrointestinal tumors and in human secretions defined by a monoclonal antibody.

A new marker for human secretory epithelial cell types (Exo-1) has been defined by a mouse monoclonal antibody (Pa-G14). The antibody was raised against a human exocrine pancreatic tumor cell line (Capan-1) and tested against 46 cultured human cell types and 228 freshly frozen human tissue sections. It reacted specifically with 28 normal and 55 secretory neoplastic epithelial tissues tested. Eleven different secretory epithelial cell types expressed this antigen, as well as human fetal tissues of the gut and bronchi. One hundred and twenty samples of normal tissues, cells, and tumors of nonexocrine origin were Exo-1 negative. In normal secretory tissues staining was most pronounced at the apical poles and as shown by immunoelectron microscopy in the case of the duodenum, at the microvilli. In cultured Exo-1 positive tumor cells the antigen was not demonstrable on the cell surface but in the cytoplasm after acetone/methanol fixation only. The antigen was identified biochemically as a polar neutral glycolipid and detected in human salivary, bronchial, pancreatic, and intestinal secretions by an enzyme-linked immunosorbent assay, but was not found in sera of healthy controls or patients with gastrointestinal and other tumors. Antigen Exo-1 represents a novel common antigen for normal and tumorous glandular epithelial cells.

Melanoma-associated gangliosides in the fish genus Xiphophorus.

Gangliosides from benign and malignant melanomas and from normal skin of the fish genus Xiphophorus were isolated and analyzed by thin-layer chromatography. Individual ganglioside components were characterized by mapping according to their sialic acid content and by cleavage with neuraminidases. In all three tissues examined, sulfatide and the gangliosides NeuAc-GalCer (GM4), II3NeuAc-LacCer (GM3), II3NeuAc-GgOse3Cer (GM2), and II3(NeuAc)2-LacCer (GD3) were found. Ganglioside GD3 yielded a positive reaction, following immunoadsorption with mouse monoclonal antibody R24 on thin-layer plates. Two alkali-labile disialoganglioside species were specifically recognized by mouse monoclonal antibody D1.1, thus indicating the presence of O-acetyl-neuraminic acid residues. One of them, a major ganglioside component of the malignant melanoma, was identified as O-acetyl-GD3, since it could be converted to the R24-positive GD3 ganglioside after alkaline saponification. The other one appears to be restricted to the malignant tumor and represents a novel melanoma-associated ganglioside derivative. It was characterized as O-acetyl(NeuAc)2-nLc4Cer by exoglycosidase cleavage, by proving its neutral carbohydrate backbone as type II-chain lacto-series oligosaccharide using mouse monoclonal antibody 1B2, and by its cross-reaction with antibody R24 following alkaline treatment. Using antibody R24 and cryopreserved tissue sections of both benign and malignant amelanotic melanomas from albino fishes, it was demonstrated that one of the main melanoma-associated gangliosides, GD3, was exposed predominantly in the malignant tumor. Thus, the chemical nature and even the immunohistochemical localization of the gangliosides in fish melanomas proved to be very similar to those of the known gangliosides in the phylogenetically distant human melanomas.

Immunohistochemical localization of ganglioside GD3 in human malignant melanoma, epithelial tumors, and normal tissues.

The specific tissue distribution of melanoma-associated ganglioside II3-alpha-N-acetylneuraminosyl-alpha 2----8-N-acetylneuraminosyllactosylceramide (GD3) was studied on 175 cryopreserved, unfixed human tissue sections with R-24 mouse monoclonal antibody by indirect immunoperoxidase staining. A striking specificity of monoclonal antibody R-24 for malignant melanoma tissues was established. Ganglioside GD3 was detected in all 21 tissue sections of 21 patients with primary melanoma and in all 37 probes of 24 patients with metastatic malignant melanoma. The majority of tumor cells in the samples of primary malignant melanoma expressed GD3; however, GD3 expression was more heterogeneous in samples of metastatic lesions even in different metastases of the same patient. Of 11 nevi, 9 reacted with monoclonal antibody R-24, while melanocytes in the basal layer of normal skin stained only weakly and irregularly. None of the 32 normal and 12 fetal human tissue types were R-24 positive, but a strong cytoplasmic staining was observed with single cells in the dermis and in the interstitial tissue of the gastrointestinal tract, in the interlobular septa of the thymus, and in other distinct locations. Only two malignant carcinoid tumors of 38 nonmelanomatous tumors tested reacted with monoclonal antibody R-24.

A common epithelial cell surface antigen (EPM-1) on gastrointestinal tumors and in human sera.

A common epithelial cell surface marker (EPM-1) was defined by two monoclonal antibodies (Pa-25 and Pa-42), raised against a pancreatic tumor cell line (Capan-1). Both monoclonal antibodies were tested on 49 cultured human cell lines and 244 tissue samples and reacted with all 76 tissue samples of 20 different normal epithelial cell types and with 57 of 63 epithelial tumor tissue samples of nonendocrine origin. Included were eight exocrine pancreatic carcinomas. There the percentage of EPM-1 positive tumor cells correlated with tumor grading. EPM-1 was detectable on the cell surface of cultured human cell lines of the pancreas, liver, colon, and mamma. Some epithelial tumor cell lines did not express EPM-1 on the cell surface, but in the cytoplasm. 100 nonepithelial and epithelial endocrine tissue samples as well as 25 nonepithelial cultured tumor and normal cells were unreactive with monoclonal antibodies Pa-25 and Pa-42. These included cells of neuronal, endocrine, and mesenchymal origin. EPM-1 activity was purified from pancreas tumor cells Capan-1 and from human sera by high-performance liquid chromatography and its molecular weight amounts to about Mr 400,000. EPM-1 was detectable in bronchial, intestinal, and pancreatic secretions and saliva and serum by an enzyme-linked immunosorbent assay test. EPM-1 values were high in the sera of normal individuals, but low or not detectable in most sera (21 of 31) of patients with gastrointestinal tumors. EPM-1 represents a novel differentiation marker for epithelial cell types, which should have a central role in the biology of normal and tumorous epithelial cells.

An amplification unit in human melanoma cells showing partial homology with sequences of human papillomavirus type 9 and with nuclear antigen 1 of the Epstein-Barr virus.

By partial homology with the DNA of human papillomavirus type 9 a cellular amplification unit was detected which is amplified in melanoma cells but not in Epstein-Barr virus-transformed B cells of two melanoma patients. A 2.4-kilobase EcoRI fragment of this amplification unit was cloned and designated mel/HPV9. At the chromosomal level we detected mel/HPV9 in homogeneously staining regions or in abnormally banded regions containing different marker chromosomes of both melanoma cell lines. DNA sequence analysis of a part of mel/HPV 9 revealed homology with the third internal repeat array of Epstein-Barr virus nuclear antigen 1.

Expression of epithelial antigens Exo-1 and EPM-1 in human epidermal keratinocyte maturation and benign and malignant neoplasia.

Exo-1, a polar neutral glycolipid, and EPM-1, a high molecular weight glycoprotein, are developmental antigens of human epithelial cells, initially described as components both on the cell surface and in secretions of gastrointestinal epithelial and respective tumors. In order to assess the biological significance of both antigens for epithelial cell differentiation and neoplastic transformation, their expression during human skin development and benign and malignant neoplasia was analyzed in fresh frozen tissue specimens of skin biopsies and of human epidermal keratinocytes growing in experimental model systems. Antigen expression was assessed immunohistochemically with specific monoclonal antibodies. During fetal development Exo-1 was temporarily expressed in intermediate cells but was absent in normal adult human skin. Exo-1 expression reemerged in neoplasias, both benign and malignant, but was restricted to spinous-like differentiated cells. Similarly, Exo-1 was not expressed in transplants of normal keratinocytes mimicking the normal epidermis but was clearly visible in differentiated areas of transplants of malignantly transformed keratinocytes. EPM-1 appeared first in basal epidermal cells in the second half of gestation and remained detectable in the stratum basale of adult skin. While squamous cell carcinomas continued to express EPM-1, it was not detectable in basal cell epitheliomas and in normal epidermis after invasion by neuroectodermal tumor cells. In experimental models, EPM-1 was present in the basal layers of normal human keratinocytes and of transformed keratinocytes with benign growth characteristics whenever a well stratified and keratinized epidermis-like epithelium had formed in transplants. In transformed keratinocytes with malignant growth behavior, EPM-1 was expressed irregularly, as in squamous cell carcinomas in situ. Thus, expression of Exo-1 is a marker for an early embryonic differentiation pathway of human keratinocytes and in adult tissue reveals abnormal differentiation associated with certain stages of hyperproliferation. EPM-1 expression is part of developmental programs and is influenced by microenvironmental interactions and alterations of tissue homeostasis.

Modified Bova score for risk stratification and short-term outcome in acute pulmonary embolism.

INTRODUCTION: Risk stratification in acute pulmonary embolism (PE) is crucial to identify those patients with a poorer prognosis. We aimed to investigate a modified Bova score for risk stratification in acute PE. MATERIALS AND METHODS: We performed a retrospective analysis of PE patients treated in the internal medicine department. Both haemodynamically stable and unstable PE patients, ≥ 18 years with measurements of cardiac troponin I (cTnI) and existing echocardiography were included in the analysis. RESULTS: Data from 130 patients were included for this retrospective analysis. Three patients (2.3%) died in hospital; 84 patients had a Bova score of < 4 points and 46 ≥ 4 points. PE patients with a score ≥ 4 points were older (71.2 ± 13.8 vs. 66.3 ± 15.5 years, p = 0.0733), died more frequently during the in-hospital course (6.5% vs. 0.0%, p = 0.0183), had a more prevalent high-risk PE status (10.9% vs. 1.2%, p = 0.0122), more often had right ventricular dysfunction (100.0% vs. 35.7%, p < 0.000001), presented more frequently with syncope/collapse (21.7% vs. 3.6%, p = 0.00101) and had a higher heart rate (104.6 ± 23.5 vs. 90.0 ± 20.6/min, p = 0.000143), shock index (0.91 ± 0.59 vs. 0.62 ± 0.18, p = 0.000232), cTnI (0.36 ± 0.42 vs. 0.03± 0.10ng/ml, p < 0.000001) and creatinine (1.32 ± 0.50 vs. 1.03 ± 0.27 mg/dl, p = 0.000170). Adjusted multivariate logistic regressions revealed significant associations between the Bova score and in-hospital death (OR 4.172, 95% CI 1.125-15.464, p = 0.0326) as well as pneumonia based on PE-related lung infarction (OR 1.207, 95% CI 1.005-1.449, p = 0.0442). ROC analysis for Bova score predicting in-hospital death and pneumonia based on PE-related lung infarction showed area under the curve values of 0.908 and 0.606 with Bova score cut-off values of 3.5 points and 1.5 points, respectively. CONCLUSIONS: The modified Bova score is highly effective to predict poorer outcome in acute PE.

Proliferation of gastrointestinal carcinoma cells by T lymphocyte factors interleukin-3 and granulocyte-macrophage colony-stimulating factor.

Hematopoietic growth factors have been well characterized by cDNA cloning in recent years. In order to determine the influence of rhGM-CSF and rhIL-3 on epithelial cells of the gastrointestinal tract, their influence on in vitro cultured gastric and pancreas cancer cells was determined. A more than two-fold enhancement of proliferation was observed by IL-3 and GM-CSF in Mz-Sto-1 gastric and 818-4 pancreas carcinoma cells, applying a sensitive microculture system which allows precise quantification. The highest growth rates were obtained adding 1-10 ng/ml of the growth factors, but even picogram amounts were effective. Expression of mRNA for GM-CSF and IL-3 remained undetectable in the cell lines, but mRNA for the EGF receptor was demonstrated. However, IL-3 and GM-CSF did not up-regulate mRNA for the EGF receptor. Therefore, the hematopoietic growth factors IL-3 and GM-CSF stimulate proliferation of epithelial cells derived from gastric and pancreas carcinomas by a paracrine mechanism. This effect did not involve an up-regulation of EGF receptor mRNA.

Immunorecognition of ganglioside epitopes: correlation between affinity and cytotoxicity of ganglioside antibodies.

Cell-surface gangliosides have immunomodulatory effects that are presumed to play a role in tumour growth, progression, metastasis and therapy. To study the epitopes of gangliosides on human malignant melanomas and to search for monoclonal antibodies (Mabs) with superior immunological effector functions, 19 ganglioside antibodies were established. Specificity and affinity of nine antibodies of IgG3 isotype were evaluated by enzyme linked immunosorbent assay and thin layer chromatography with a panel of purified gangliosides. All antibodies recognised the ganglioside GD3, but their epitope specificity divided them into five groups. Their affinity constants for ganglioside GD3 ranged from 4.7 x 10(6) to 2.3 x 10(8), with 2 x 10(7) for Mab R-24. Two antibodies possessed a higher affinity for GD2 than for GD3. The functional properties of the antibodies were investigated in vitro. Differences in the degree of tumour lysis by complement fixation correlated with the affinity constants. Every ganglioside antibody differed in epitope recognition, affinity and cytotoxicity. Therefore some of these antibodies might even be more useful in the immunotherapy of malignant melanoma than Mab R-24.

Immunological response to intrathecal and systemic treatment with ganglioside antibody R-24 in patients with malignant melanoma.

Murine monoclonal antibody (MAb) R-24 reacts with the ganglioside GD3 that is highly expressed on malignant melanoma. 2 patients with melanosis of the meninges received MAb R-24 intrathecally. Regressive changes in tumour cells were observed in both patients after intrathecal application of MAb R-24 (1-10 mg, 8-10 h, over 5-6 weeks). The first patient suffered from brain metastases and died a few weeks later, whereas the second achieved a complete remission with no evidence of disease 6 years after intrathecal R-24 treatment. No R-24-related neurotoxicity has occurred to date. The administration of MAb R-24 caused an increase of inflammatory cells in the cerebrospinal fluid (CSF) of both patients. Cytotoxic lymphocytes, cultured from the CSF, showed high cytolytic activity against allogeneic melanoma cells in vitro. In addition, 15 patients with advanced melanoma, in which the brain was not affected, were treated with R-24 intravenously using high dose R-24 (5 or 10 mg/m2) or low dose R-24 (1 mg/m2). No remissions were registered in the high dose group, with only 1/6 patients experiencing a mixed response. In contrast, 2/9 patients treated with low dose R-24 achieved a partial remission, one achieving a minor response and the other a mixed response. Toxicity was related to the dose of R-24 administered. Urticaria, burning and pruritus were the prominent side-effects, mostly occurring at the high dose level. Immunological monitoring during and after intravenous treatment showed no significant changes in peripheral blood lymphocytes, natural killer cell activity or antibody-dependent cellular cytotoxicity, although transient changes were observed. There was no correlation between immunological parameters and clinical response.

CEA-immunoscintigraphy with 99m-technetium correlates with tumour cell differentiation in colorectal cancer.

The clinical usefulness of immunoscintigraphy with the monoclonal anti-CEA (carcinoembryonic antigen) antibody BW431/26, directly labelled with 99m-Technetium in targeting colorectal carcinomas was investigated in 43 patients. In addition, tumour cell grading and CEA-expression were examined immunohistochemically. Best imaging results were obtained in pelvic tumour lesions (sensitivity 80%). Tumour grading correlated with radioimmunoimaging, well differentiated tumours being detectable at a higher rate (P = 0.09). Immunoscintigraphy preceded the findings of conventional diagnostic methods in 3 patients. In 4 cases immunoscintigraphy was decisive for patients management. Therefore, immunoscintigraphy with 99m-Technetium is valuable in directing patients management if conventional diagnostic methods remain undecisive.

Expression of epithelial antigens EPM-1 and EXO-1 in normal, transitional, inflammatory and neoplastic colorectal mucosa.

EPM-1 (a high molecular weight glycoprotein) and EXO-1 (a carbohydrate epitope expressed on polar neutral glycolipids and mucins) are two developmental antigens of normal and neoplastic human epithelia and were characterised by monoclonal antibodies. Their distribution was investigated in normal and pathological human colorectal mucosa. In normal mucosa, EPM-1 and EXO-1 showed characteristic expression patterns. EPM-1 was differentially expressed along the crypt villus axis with maximum at the crypt basis. EXO-1 was present throughout the whole mucosa. The characteristic gradient of EPM-1 expression along the crypt axis in normal mucosa was no longer detectable in benign polyps. Intact gradient of EPM-1 staining discriminated between neoplastic changes of the benign adenomatous polyp and mucosal inflammation. Neoplastic mucosa in benign polyps and especially atypical glands in highly differentiated tumours showed essentially identical expression patterns. In colorectal carcinomas the overall reactivities for EPM-1 and EXO-1 were independently associated with the histopathological grade of tumour differentiation.

Expression and regulation by interferon-gamma of the membrane-bound complement regulators CD46 (MCP), CD55 (DAF) and CD59 in gastrointestinal tumours.

The membrane-bound complement inhibitors CD46 (membrane cofactor protein), CD55 (decay-accelerating factor) and CD59 (protectin) protect tumour cells against lysis by activated complement. In this study, a total of 14 (3 gastric, 3 colonic and 8 pancreatic) gastrointestinal tumour cell lines were examined for the expression of CD46, CD55 and CD59 with respect to the regulatory efficacy of interferon-gamma (IFN-gamma). The effects of IFN-gamma on mRNA and protein expression levels of CD46, CD55 and CD59 were evaluated by Northern blot hybridisation, RT-PCR, flow cytometry and immunostaining. In unstimulated cell lines, CD46 and CD59 transcripts were expressed at comparable levels, whereas the basal expression of CD55 mRNA was heterogeneous. The complement inhibitor proteins were detected in all cell lines using specific antibodies. Additional immunohistochemical stainings of gastrointestinal tissue specimens supported these findings. IFN-gamma evoked a weak induction of certain transcripts in a subset of the cell lines. Upregulation of protein expression was only observed in HT29 cells for CD55 and CD59 and was accompanied by a marked increase of the corresponding transcripts. We conclude that membrane-bound complement inhibitors are broadly expressed in gastrointestinal tumour cells and vary in their susceptibility to IFN-gamma. Thus, they may be involved in tumour escape mechanisms in gastric, pancreatic and colorectal cancer.