Brain metastases in gastro-oesophageal adenocarcinoma: insights into the role of the human epidermal growth factor receptor 2 (HER2).

BACKGROUND: Gastro-oesophageal adenocarcinomas rarely metastasize to the central nervous system (CNS). The role of the human epidermal growth factor receptor 2 (HER2) in patients with these cancers and CNS involvement is presently unknown. PATIENTS AND METHODS: A multicentre registry was established to collect data from patients with gastro-oesophageal adenocarcinomas and CNS involvement both retrospectively and prospectively. Inclusion in the study required a predefined clinical data set, a central neuro-radiological or histopathological confirmation of metastatic CNS involvement and central assessment of HER2 by immunohistochemistry (IHC) and in situ hybridisation (ISH). In addition, expression of E-cadherin and DNA mismatch repair (MMR) proteins were assessed by IHC. RESULTS: One hundred patients fulfilled the inclusion criteria. The population's median age was 59 years (interquartile range: 54-68), of which 85 (85%) were male. Twenty-five patients were of Asian and 75 of Caucasian origin. HER2 status was positive in 36% (95% CI: 26.6-46.2) of cases. Median time from initial diagnosis to the development of brain metastases (BMets) or leptomeningeal carcinomatosis (LC) was 9.9 months (95% CI: 8.5-15.0). Median overall survival from diagnosis was 16.9 months (95% CI: 14.0-20.7) and was not related to the HER2 status. E-cadherin loss was observed in 9% of cases and loss of expression in at least one DNA MMR proteins in 6%. CONCLUSIONS: The proportion of a positive HER2 status in patients with gastro-oesophageal adenocarcinoma and CNS involvement was higher than expected. The impact of anti-HER2 therapies should be studied prospectively.

Uncommon case of brain metastasis in a patient with a history of heavy smoking.

Primary sarcomas of the aorta are extremely uncommon. Depending on histomorphology and immunohistochemical pattern, intimal sarcomas can show angiosarcomatous differentiation. Here, we describe the case of a 60-year-old woman with a primary intimal sarcoma of the aortic arch and signs of cerebral metastatic disease as the initial manifestation. After the patient experienced the onset of severe headaches, ataxia, and left-sided weakness, magnetic resonance imaging showed several brain lesions. Histologic assessment of a brain biopsy specimen revealed a malignant tumour composed of large pleomorphic cells that were positive for pancytokeratin and CD10. Radiation to the brain did not significantly improve the patient's symptoms, and cranial computed tomography (ct) imaging revealed several metastases, indicating lack of response. Because of the patient's smoking history, the presence of central nervous system and skeletal metastases on combined positron-emission tomography and ct imaging, and the focal pan-cytokeratin positivity of the tumour, carcinoma of the lung was favoured as the primary tumour. Despite chemotherapy with cisplatin and etoposide, the patient's neurologic symptoms and general condition deteriorated rapidly, and she died within a few days. At autopsy, an undifferentiated intimal sarcoma of the aortic arch was diagnosed. The primary tumour in the aorta consisted of large pleomorphic cells. Immunohistochemical analysis of the aortic tumour and brain metastases demonstrated diffuse positivity for vimentin and p53 and focal S-100 staining. In summary, we report a challenging case of advanced intimal sarcoma of the aortic arch with brain and bone metastases at initial presentation. Our report demonstrates the difficulties in diagnosing and treating this disease, and the need for multicentre studies to accrue more patients for investigations of optimal therapy.

Gemcitabine and Cisplatin Versus Methotrexate, Vinblastine, Doxorubicin, and Cisplatin in Advanced or Metastatic Bladder Cancer: Results of a Large, Randomized, Multinational, Multicenter, Phase III Study.

PURPOSE: Gemcitabine plus cisplatin (GC) and methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) were compared in patients with locally advanced or metastatic transitional-cell carcinoma (TCC) of the urothelium. PATIENTS AND METHODS: Patients with stage IV TCC and no prior systemic chemotherapy were randomized to GC (gemcitabine 1,000 mg/m2 days 1, 8, and 15; cisplatin 70 mg/m2 day 2) or standard MVAC every 28 days for a maximum of six cycles. RESULTS: Four hundred five patients were randomized (GC, n = 203; MVAC, n = 202). The groups were well-balanced with respect to prognostic factors. Overall survival was similar on both arms (hazards ratio [HR], 1.04; 95% confidence interval [CI], 0.82 to 1.32; P = .75), as were time to progressive disease (HR, 1.05; 95% CI, 0.85 to 1.30), time to treatment failure (HR, 0.89; 95% CI, 0.72 to 1.10), and response rate (GC, 49%; MVAC, 46%). More GC patients completed six cycles of therapy, with fewer dose adjustments. The toxic death rate was 1% on the GC arm and 3% on the MVAC arm. More GC than MVAC patients had grade 3/4 anemia (27% v 18%, respectively) and thrombocytopenia (57% v 21%, respectively). On both arms, the RBC transfusion rate was 13 of 100 cycles and grade 3/4 hemorrhage or hematuria was 2%; the platelet transfusion rate was four patients per 100 cycles and two patients per 100 cycles on GC and MVAC, respectively. More MVAC patients, compared with GC patients, had grade 3/4 neutropenia (82% v 71%, respectively), neutropenic fever (14% v 2%, respectively), neutropenic sepsis (12% v 1%, respectively), and grade 3/4 mucositis (22% v 1%, respectively) and alopecia (55% v 11%, respectively). Quality of life was maintained during treatment on both arms; however, more patients on GC fared better regarding weight, performance status, and fatigue. CONCLUSION: GC provides a similar survival advantage to MVAC with a better safety profile and tolerability. This better-risk benefit ratio should change the standard of care for patients with locally advanced and metastatic TCC from MVAC to GC.

Selective intra-arterial chemotherapy with floxuridine as second- or third-line approach in patients with unresectable colorectal liver metastases.

BACKGROUND: An outcome assessment was performed of patients with unresectable colorectal liver metastases (CRLM) treated in second or third line with floxuridine (FUDR)-based hepatic artery infusion (HAI). METHODS: Twenty-three patients who were pretreated with systemic (immuno)chemotherapy received FUDR-HAI alone or combined with systemic chemotherapy. We reviewed patient charts and our prospective patient database for survival and associated risk factors. RESULTS: Patients received FUDR-HAI for unresectable CRLM from January 2000 to September 2010. Twelve patients (52%) received concurrent systemic chemotherapy. Median overall survival (OS), progression-free survival (PFS), and hepatic PFS were 15.6 months (range, 2.5-55.7 months), 3.9 months (range, 0.7-55.7 months), and 5.5 months (range, 1.6-55.7 months), respectively. The liver resection rate after HAI was 35%. PFS was better in patients undergoing secondary resection than in patients without resection (hazard ratio [HR] 0.21; 95% confidence interval [95% CI] 0.07-0.66; P = 0.0034), while OS showed a trend toward improvement (HR 0.4; 95% CI 0.13-1.2; P = 0.09). No differences were observed in OS (P = 0.69) or PFS (P = 0.086) in patients who received FUDR-HAI alone compared with patients treated with combined regional and systemic chemotherapy. No statistically significant differences were seen in patients previously treated with one chemotherapy line compared with patients treated with two lines. Presence of extrahepatic disease was a negative risk factor for PFS (liver-only disease: HR 0.03; 95% CI 0.0032-0.28; P < 0.0001). Toxicities were manageable with dose modifications and supportive measures. CONCLUSIONS: FUDR-HAI improves PFS and results in a trend toward improved OS in selected patients able to undergo liver resection after tumor is downsized.

A survey of the humoral immune response of cancer patients to a panel of human tumor antigens.

Evidence is growing for both humoral and cellular immune recognition of human tumor antigens. Antibodies with specificity for antigens initially recognized by cytotoxic T lymphocytes (CTLs), e.g., MAGE and tyrosinase, have been detected in melanoma patient sera, and CTLs with specificity for NY-ESO-1, a cancer-testis (CT) antigen initially identified by autologous antibody, have recently been identified. To establish a screening system for the humoral response to autoimmunogenic tumor antigens, an enzyme-linked immunosorbent assay (ELISA) was developed using recombinant NY-ESO-1, MAGE-1, MAGE-3, SSX2, Melan-A, and tyrosinase proteins. A survey of sera from 234 cancer patients showed antibodies to NY-ESO-1 in 19 patients, to MAGE-1 in 3, to MAGE-3 in 2, and to SSX2 in 1 patient. No reactivity to these antigens was found in sera from 70 normal individuals. The frequency of NY-ESO-1 antibody was 9.4% in melanoma patients and 12.5% in ovarian cancer patients. Comparison of tumor NY-ESO-1 phenotype and NY-ESO-1 antibody response in 62 stage IV melanoma patients showed that all patients with NY-ESO-1(+) antibody had NY-ESO-1(+) tumors, and no patients with NY-ESO-1(-) tumors had NY-ESO-1 antibody. As the proportion of melanomas expressing NY-ESO-1 is 20-40% and only patients with NY-ESO-1(+) tumors have antibody, this would suggest that a high percentage of patients with NY-ESO-1(+) tumors develop an antibody response to NY-ESO-1.

Lysis of human melanoma cells by autologous cytolytic T cell clones. Identification of human histocompatibility leukocyte antigen A2 as a restriction element for three different antigens.

From the peripheral blood of the melanoma patient (AV), we derived cytolytic T lymphocyte (CTL) clones that lysed the autologous tumor line SK-MEL-29, but not autologous EBV-B cells, K562, and other tumor targets. By immunoselection experiments it was shown that the CTL clones recognized at least three different antigens on the autologous tumor cells. We demonstrate here that these melanoma antigens are presented to the CTL in association with HLA-A2. First, HLA-A2-reactive pregnancy sera as well as an mAb against HLA-A2 inhibited the CTL lysis. Second, immunoselected melanoma subclones that were resistant to lysis by CTL clones against the three antigens described were found to lack expression of HLA-A2. By sensitizing the patient's lymphocytes against an HLA-A2- melanoma clone, we established a new series of CTL clones recognizing autologous AV melanoma cells. However, efficient lysis was only seen when target cells were pretreated with IFN-gamma. The lytic activity of these CTL was selectively inhibited by an mAb against a common HLA-B determinant. These results indicate that in addition to HLA-A2, other class I antigens are involved in the recognition of AV melanoma cells by autologous CTL.

Identification of NY-ESO-1 epitopes presented by human histocompatibility antigen (HLA)-DRB4*0101-0103 and recognized by CD4(+) T lymphocytes of patients with NY-ESO-1-expressing melanoma.

NY-ESO-1 is a member of the cancer-testis family of tumor antigens that elicits strong humoral and cellular immune responses in patients with NY-ESO-1-expressing cancers. Since CD4(+) T lymphocytes play a critical role in generating antigen-specific cytotoxic T lymphocyte and antibody responses, we searched for NY-ESO-1 epitopes presented by histocompatibility leukocyte antigen (HLA) class II molecules. Autologous monocyte-derived dendritic cells of cancer patients were incubated with recombinant NY-ESO-1 protein and used in enzyme-linked immunospot (ELISPOT) assays to detect NY-ESO-1-specific CD4(+) T lymphocyte responses. To identify possible epitopes presented by distinct HLA class II alleles, overlapping 18-mer peptides derived from NY-ESO-1 were synthetized and tested for recognition by CD4(+) T lymphocytes in autologous settings. We identified three NY-ESO-1-derived peptides presented by DRB4*0101-0103 and recognized by CD4(+) T lymphocytes of two melanoma patients sharing these HLA class II alleles. Specificity of recognition was confirmed by proliferation assays. The characterization of HLA class II-restricted epitopes will be useful for the assessment of spontaneous and vaccine-induced immune responses of cancer patients against defined tumor antigens. Further, the therapeutic efficacy of active immunization using antigenic HLA class I-restricted peptides may be improved by adding HLA class II-presented epitopes.

Simultaneous humoral and cellular immune response against cancer-testis antigen NY-ESO-1: definition of human histocompatibility leukocyte antigen (HLA)-A2-binding peptide epitopes.

A growing number of human tumor antigens have been described that can be recognized by cytotoxic T lymphocytes (CTLs) in a major histocompatibility complex (MHC) class I-restricted fashion. Serological screening of cDNA expression libraries, SEREX, has recently been shown to provide another route for defining immunogenic human tumor antigens. The detection of antibody responses against known CTL-defined tumor antigens, e.g., MAGE-1 and tyrosinase, raised the question whether antibody and CTL responses against a defined tumor antigen can occur simultaneously in a single patient. In this paper, we report on a melanoma patient with a high-titer antibody response against the "cancer-testis" antigen NY-ESO-1. Concurrently, a strong MHC class I-restricted CTL reactivity against the autologous NY-ESO-1-positive tumor cell line was found. A stable CTL line (NW38-IVS-1) was established from this patient that reacted with autologous melanoma cells and with allogeneic human histocompatibility leukocyte antigen (HLA)-A2(-), NY-ESO-1-positive, but not NY-ESO-1-negative, melanoma cells. Screening of NY-ESO-1 transfectants with NW38-IVS-1 revealed NY-ESO-1 as the relevant CTL target presented by HLA-A2. Computer calculation identified 26 peptides with HLA-A2-binding motifs encoded by NY-ESO-1. Of these, three peptides were efficiently recognized by NW38-IVS-1. Thus, we show that antigen-specific humoral and cellular immune responses against human tumor antigens may occur simultaneously. In addition, our analysis provides a general strategy for identifying the CTL-recognizing peptides of tumor antigens initially defined by autologous antibody.

Risk-adapted FDG-PET/CT-based follow-up in patients with diffuse large B-cell lymphoma after first-line therapy.

BACKGROUND: The purpose of this study was to evaluate the impact of 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) during follow-up of patients with diffuse large B-cell lymphoma (DLBCL) being in complete remission or unconfirmed complete remission after first-line therapy. PATIENTS AND METHODS: DLBCL patients receiving FDG-PET/CT during follow-up were analyzed retrospectively. Confirmatory biopsy was mandatory in cases of suspected disease recurrence. RESULTS: Seventy-five patients were analyzed and 23 (30%) had disease recurrence. The positive predictive value (PPV) of FDG-PET/CT was 0.85. Patients >60 years [P = 0.036, hazard ratio (HR) = 3.82, 95% confidence interval (CI) 1.02-7.77] and patients with symptoms indicative of a relapse (P = 0.015; HR = 4.1; 95% CI 1.20-14.03) had a significantly higher risk for relapse. A risk score on the basis of signs of relapse, age >60 years, or a combination of these factors identified patients at high risk for recurrence (P = 0.041). CONCLUSIONS: FDG-PET/CT detects recurrent DLBCL after first-line therapy with high PPV. However, it should not be used routinely and if only in selected high-risk patients to reduce radiation burden and costs. On the basis of our retrospective data, FDG-PET/CT during follow-up is indicated for patients <60 years with clinical signs of relapse and in patients >60 years with and without clinical signs of relapse.

Hodgkin's lymphoma in remission after first-line therapy: which patients need FDG-PET/CT for follow-up?

BACKGROUND: The purpose of the study was to evaluate the impact of 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET)/computed tomography (CT) during follow-up of patients with Hodgkin's lymphoma. PATIENTS AND METHODS: Patients in complete remission or an unconfirmed complete remission after first-line therapy who received FDG-PET/CT during their follow-up were analyzed retrospectively. Confirmatory biopsy was mandatory in case of recurrence. RESULTS: Overall, 134 patients were analyzed. Forty-two (31.3%) patients had a recurrence. The positive predictive value of FDG-PET/CT was 0.98. Single-factor analysis identified morphological residual mass [P = 0.0005, hazard ratio (HR) 3.4, 95% confidence interval (CI) 1.7-6.6] and symptoms (P < 0.0001, HR 4.9, 95% CI 2.4-9.9) as significant risk factors for relapse. By multivariate analysis, morphological residual mass was the only significant risk factor for early follow-up (<24 months) (P = 0.0019, HR 7.6, 95% CI 2.1-27.3). Advanced stage (P = 0.0426, HR 3.6, 95% CI 1.1-12.3) and the presence of symptoms (P = 0.0009, HR = 14.6, 95% CI 3.0-69.7) were found to be significant risk factors for later follow-up (>24 months). CONCLUSIONS: Asymptomatic patients without morphological residues and an early stage of disease do not need a routine FDG-PET/CT for follow-up. Asymptomatic patients with morphological residues should receive routine follow-up FDG-PET/CT for the first 24 months. Only patients with advanced initial stage do need a routine follow-up FDG-PET/CT beyond 24 months.

A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma.

Many human melanoma tumors express antigens that are recognized in vitro by cytolytic T lymphocytes (CTLs) derived from the tumor-bearing patient. A gene was identified that directed the expression of antigen MZ2-E on a human melanoma cell line. This gene shows no similarity to known sequences and belongs to a family of at least three genes. It is expressed by the original melanoma cells, other melanoma cell lines, and by some tumor cells of other histological types. No expression was observed in a panel of normal tissues. Antigen MZ2-E appears to be presented by HLA-A1; anti-MZ2-E CTLs of the original patient recognized two melanoma cell lines of other HLA-A1 patients that expressed the gene. Thus, precisely targeted immunotherapy directed against antigen MZ2-E could be provided to individuals identified by HLA typing and analysis of the RNA of a small tumor sample.

MAGE-C1/CT-7 expression in plasma cell myeloma: sub-cellular localization impacts on clinical outcome.

Plasma cell myelomas (PMs) have a poor prognosis. Cancer-testis (CT) antigens are immunogenic proteins, representing potential targets for tumor vaccination strategies. The expression of the CT antigens GAGE, MAGE-A4, MAGE-C1/CT-7, and NY-ESO-1 was investigated on paraffin-embedded bone marrow biopsies from 219 PM and 8 monoclonal gammopathy of undetermined significance (MGUS) patients. The frequency and prognostic impact of these CT antigens were compared with known morphological prognostic markers (i.e. Mib1 labeling index) and the presence of the translocations t(4;14)(p16.3; q32) and t(11;14)(q13;q32). We show that MAGE-C1/CT-7 is the most prevalent CT antigen, expressed in 57% of PMs in a high percentage of tumor cells. While MAGE-C1/CT-7 was absent in non-malignant plasma cells, plasma cells of patients with MGUS did express MAGE-C1/CT-7, but no other CT antigens. MAGE-C1/CT-7 was more frequently expressed in PMs with an elevated proliferation rate (Mib1 >10%) compared to PMs with a low proliferation rate (Mib1

Cellular and humoral immune responses against cancer: implications for cancer vaccines.

The key issue in tumor immunology is to identify antigens as target structures for a cancer-selective immunological attack in the tumor-bearing host, resulting in tumor rejection. There is a growing detailed understanding of structural and regulatory gene alterations giving rise to candidate rejection antigens and peptides in tumor cells. As well as reviewing the development of new adjuvant and recombinant vector systems, new approaches are suggested for the construction of cancer vaccines.

[Molecular targeted therapy]. / Molekular zielgerichtete Therapie.

Until recently, cancer therapy was based on three modalities: surgery, radiotherapy, and cytostatic chemotherapy. In most instances treatment of solid tumors was a surgical domain. For patients with incomplete resection or relapse after surgery, radiotherapy and chemotherapy usually offered only partial response and mostly of limited duration. By the mid-1990s visions of antibody-based therapies, vaccination strategies, and even gene-specific therapies existed but seemed far from clinical practice. United States Federal Drug Administration approval of the humanized antibody rituximab (1997) and the tyrosine kinase inhibitor imatinib (2001) has changed perceptions of oncologic treatment. These drugs turned visions into reality and led the pharmaceutical industry, clinicians, and patients to new perspectives. This article gives an overview of the development of this fourth modality in cancer therapy, so-called targeted therapy.

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.

Molecular analysis of the HLA-A2 antigen loss by melanoma cells SK-MEL-29.1.22 and SK-MEL-29.1.29.

Due to the potential clinical relevance of HLA class I antigen losses in melanoma cells and the scanty information about the molecular mechanisms underlying these defects, we have characterized the cause of the HLA-A2 antigen loss by autologous melanoma cell lines SK-MEL-29.1.22 and SK-MEL-29.1.29. Both cell lines have structural defects of HLA-A2 genes, which cause lack of their transcription. In SK-MEL-29.1.22 cells the 5'-flanking region, exon 1, intron 1, and a region at the 5' end of exon 2 of the HLA-A2 gene are deleted. The breakpoint of the HLA-A2 gene, which is recombined with a DNA fragment of unknown origin, was localized between two GTTCG sequence repeats at position 101 of exon 2. These repeats may provide the sequence basis for misalignment in the process of DNA deletion. In SK-MEL-29.1.29 cells, loss of HLA-A2 antigens, as well as of HLA-B44 and HLA-Cw5 alleles, is caused by the loss of one copy of chromosome 6. Down-regulation of the expressed HLA class I alleles in the two HLA-A2 loss variants and in the parental cells was found to be associated with a low TAP1 expression and a reduced function of peptide transporters. Therefore, multiple defects result in loss or down-regulation of HLA class I alleles in SK-MEL-29.1.22 and SK-MEL-29.1.29 melanoma cells.

Analysis of the major histocompatibility complex class I antigen presentation machinery in normal and malignant renal cells: evidence for deficiencies associated with transformation and progression.

In some human tumors, reduced or defective MHC class I surface expression has been attributed to functional deficiencies of the genes of the antigen-processing machinery, the proteasome subunits low molecular weight (LMP)-2 and LMP-7, as well as the peptide transporters associated with antigen processing (TAP)-1 and TAP-2. Using normal epithelial kidney cells (MZ1851NN) and renal cell carcinoma cell lines established from the primary tumor (MZ1851RC) and a lymph node metastasis (MZ1851LN) of the same patient, we investigated whether the modulation of MHC class I antigens, TAP and LMP molecules, occurs during transformation and subsequent progression. The mRNA and protein expression of MHC class I heavy and light chain TAP and LMP was strongly reduced in MZ1851RC when compared to the corresponding normal kidney cells MZ1851NN, and this suppression was even more pronounced in the metastatic cell line MZ1851LN. In addition, the activity of the TAP molecules, as measured by peptide translocation assays, was also markedly diminished in MZ1851RC compared to MZ1851NN cells and was further down-regulated in cells of the metastatic lesion. MHC class I surface expression was enhanced by either culturing MZ1851RC and MZ1851LN cells at 26 degrees C instead of 37 degrees C or by incubation of both cell lines with class I-specific binding peptides, whereas MHC class I surface expression of MZ1851NN cells was not affected under these culture conditions. IFN-alpha and in particular IFN-gamma treatment enhances the steady-state mRNA and/or protein levels of TAP, LMP, and MHC class I genes of MZ1851 cell lines but had no additional effect on the stability of MCH class I surface expression. These data indicate that malignant transformation and subsequent in vivo selection of renal tubular cells can lead to the recovery of carcinoma cells that show stable expression of an immune escape phenotype. Deficiencies associated with this phenotype involve all levels of the MHC class I-restricted antigen presentation machinery, are at least partially reversible by IFN treatment, and are even more pronounced in cells that had acquired metastatic potential.

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.