lewis-x-antigen and Prostatic-Neoplasms

Nuclear texture reflects the overall structures of the chromatin organization. We recently reported the principles and prognostic importance of image analysis of nuclei from metastatic prostate cancer. Immunohistochemical up regulation of the adhesion molecule sialyl Lewis(x) is also reported to be a prognostic parameter. Presently we analyzed statistically the prognostic impact of these 2 new parameters compared to well-known clinical parameters in metastatic prostate cancer.. Prognostic factors, such as sedimentation rate, alkaline and acid phosphatases, hemoglobin, testosterone, performance status, pain due to metastasis, T category, histological grade and patient age, were included in a multivariate Cox proportional hazards regression analysis based on 262 patients from the Scandinavian Prostatic Cancer Group Study-2. Extent of bone lesions, deoxyribonucleic acid ploidy, texture analysis and sialyl Lewis(x) molecules based on subsets of these 262 patients were also analyzed in the same multivariate model.. This test identified chromatin texture as the most important factor (p < 0.001), followed by reaction of the oligosaccharide sialyl Lewis(x) (p < 0.01). Among the routine clinical and laboratory data, sedimentation rate, alkaline phosphatase and hemoglobin (p < 0.05) showed prognostic importance. Performance status, pain due to metastasis and extent of bone lesions showed prognostic value in the univariate analysis (p < 0.05).. These data indicate that computerized nuclear texture analysis as well as up regulation of sialyl Lewis(x) molecules may be new important prognostic factors in metastatic prostate cancer. Furthermore the prognostic importance of sedimentation rate, alkaline phosphatase and hemoglobin was confirmed.

Topics: Aged; Humans; Lewis X Antigen; Male; Middle Aged; Multivariate Analysis; Neoplasm Metastasis; Neoplasm Staging; Oligosaccharides; Prognosis; Proportional Hazards Models; Prospective Studies; Prostatic Neoplasms; Retrospective Studies; Sialyl Lewis X Antigen; Survival Rate

Prostate-specific antigen (PSA) is the most frequently used biomarker for the screening of prostate cancer. Understanding the structure of cancer-specific glycans can help us improve PSA assay. In the present study, we analysed the glycans of PSA obtained from culture medium containing cancer tissue-originated spheroids (CTOS) which have similar characteristics as that of the parent tumour to explore the new candidates for cancer-related glycoforms of PSA. The glycan profile of PSA from CTOS was determined by comparing with PSA from normal seminal plasma and cancer cell lines (LNCaP and 22Rv1) using lectin chromatography and mass spectrometry. PSA from CTOS was mostly sialylated and the content of Wisteria floribunda agglutinin reactive glycan (LacdiNAc) was similar to that of PSA derived from seminal plasma and 22Rv1. Conversely, concanavalin A (Con A)-unbound PSA was definitely detected from the three cancer origins but was almost negligible in seminal PSA. Two novel types of PSA were elucidated in the Con A-unbound fraction: one is a high molecular weight PSA with highly branched N-glycans, and the other is a low molecular weight PSA without N-glycans. Furthermore, the existence of Lewis X antigen group on PSA was indicated. These PSAs will be candidates for new cancer-related markers.

Topics: Biomarkers, Tumor; Carbohydrate Sequence; Cell Line, Tumor; Chromatography, Affinity; Concanavalin A; Culture Media, Conditioned; Glycopeptides; Glycosylation; Humans; Lewis X Antigen; Male; Plant Lectins; Polysaccharides; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Processing, Post-Translational; Receptors, N-Acetylglucosamine; Semen; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Spheroids, Cellular

Myeloid-derived suppressor cells with polymorphonuclear morphology (PMN-MDSCs) contribute to the progression and immune evasion of prostate cancer. However, the spatial distribution of tumor-infiltrating PMN-MDSCs in primary and metastatic prostate cancer, especially in the context of comparison between the epithelial and stromal compartments of the tumor, has not been characterized. Here, we describe a multicolor immunofluorescence staining study of 90 primary tumors, 37 lymph node metastases (all with matched primary tumors) and 35 bone metastases using archived samples. CD11b

Topics: Age Factors; Biomarkers, Tumor; CD11b Antigen; Cell Movement; Humans; Immunohistochemistry; Lewis X Antigen; Lymphatic Metastasis; Male; Myeloid-Derived Suppressor Cells; Neoplasm Metastasis; Neutrophils; Prostatic Neoplasms; Retrospective Studies; Staining and Labeling; Tumor Microenvironment

Protein glycosylation is a common posttranslational modification and glycan structural changes have been observed in several malignancies including prostate cancer. We hypothesized that altered glycosylation could be related to differences in gene expression levels of glycoprotein synthetic enzymes between normal and malignant prostate tissues.. We interrogated prostate cancer gene expression data for reproducible changes in expression of glycoprotein synthetic enzymes. Over-expression of GCNT1 was validated in prostate samples using RT-PCR. ELISA was used to measure core 2 O-linked glycan sialyl Lewis X (sLe(x) ) of prostate specific antigen (PSA), Mucin1 (MUC1), and prostatic acidic phosphatase (PAP) proteins.. A key glycosyltransferase, GCNT1, was consistently over-expressed in several prostate cancer gene expression datasets. RT-PCR confirmed increased transcript levels in cancer samples compared to normal prostate tissue in fresh-frozen prostate tissue samples. ELISA using PSA, PAP, and MUC1 capture antibodies and a specific core 2 O-linked sLe(x) detection antibody demonstrated elevation of this glycan structure in cancer compared to normal tissues for MUC1 (P = 0.01), PSA (P = 0.03) and near significant differences in PAP sLe(x) levels (P = 0.06). MUC1, PSA and PAP protein levels alone were not significantly different between paired normal and malignant prostate samples.. GCNT1 is over-expressed in prostate cancer and is associated with higher levels of core 2 O-sLe(x) in PSA, PAP and MUC1 proteins. Alterations of O-linked glycosylation could be important in prostate cancer biology and could provide a new avenue for development of prostate cancer specific glycoprotein biomarkers.

Topics: Acid Phosphatase; Aged; Glycosylation; Humans; Lewis X Antigen; Male; Middle Aged; Mucin-1; N-Acetylglucosaminyltransferases; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Tyrosine Phosphatases; Sialyl Lewis X Antigen

There are many molecular tumor markers for diagnosing and monitoring cancer patients. Especially, quantitative assay for serum levels of tumor markers; such as AFP, CEA, PSA, hCG, CA 19-9 and CA 125, are frequently used in daily practice because of their relative specificities and usefulness to the common cancers. Though not suitable for early diagnosis, but they are used in monitoring patients with advanced caner, especially after treatments. Two of them, AFP and PSA, are also used in the screening and monitoring of high-risk groups, namely patients with chronic viral hepatitis and old male, who are the high risk for hepatoma and proste cancer respectively. Problems in using serum markers are; relatively low specificity and low sensitivity to cancer, confusing naming for similar markers that recognize almost the same molecule of cancer. Users must understand that CA 19-9, CA 50, KM-O 1 and SPAN-1 are in the same sialylated Lewis A group, and CA 125, CA 130 and CA 602; in the mucin antigen group, and STN, CA 54/61 and CA 72-4; in the sialyl Tn antigen group. Combination of two or more markers may inform us the biological characteristics of the cancer. For example, a germ-cell tumors may produce hCG and placental marker. That is of the choriocarcinoma type. Those with hCG and fetal antigens are the ordinal type of germ cell tumors, and those with AFP, CEA and cytokeratin are teratoma, and those with LDH and ALP only but negative for hCG and AFP must be seminoma. For the bronchial and alveolar carcinomas, CEA, SCC, NSE and cytokeratin 19 fragments are useful. Combination may be difficult for beginners but once understood, it will be an art in clinical oncology.

Topics: alpha-Fetoproteins; Antigens, Neoplasm; Biomarkers; Biomarkers, Tumor; Carcinoembryonic Antigen; Diagnosis, Differential; Female; Hepatitis, Viral, Human; Humans; Keratin-19; Keratins; Lewis X Antigen; Male; Neoplasms; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Precursors; Prothrombin

Prostate tumor cells preferentially adhere to bone marrow endothelial cells (BMECs) compared with endothelial linings from other tissue microvessels, implicating the importance of BMEC adhesion in the predilection of prostate tumor metastasis to bone. E (endothelial)-selectin, which functions as an initiator of leukocyte adhesion to target tissue endothelium, is constitutively expressed on BMECs, suggesting that prostate tumor cells could use this adhesive mechanism to initiate their migration into bone. In this report, we demonstrate for the first time that human bone-metastatic prostate tumor cells roll on human BMECs under physiological flow conditions. We show that these dynamic adhesive interactions are dependent on the expression of BMEC E-selectin and sialylated glycoconjugates on bone-metastatic prostate tumor cells. We also establish the importance of both glycoprotein(s) and glycosphingolipid structures displaying sialyl Lewis X epitopes as potential E-selectin ligands on bone-metastatic prostate tumor cells. Coexpression of sialylated glycoproteins and glycolipids on bone-metastatic prostate tumor cells triggers robust E-selectin binding activity, which is identical to that observed on human hematopoietic progenitor cells. By Western blot analysis, we identify candidate E-selectin glycoprotein ligand(s); distinct sialyl Lewis X (or HECA-452 antigen)-bearing membrane proteins were resolved at M(r) 130,000 and M(r) 220,000 as well as others ranging from M(r) 100,000 to M(r) 220,000. Immunohistochemical analysis of HECA-452 antigen expression on normal prostate tissue and on low- and high-grade prostate adenocarcinoma shows that HECA-452 antigen expression is directly associated with prostate tumor progression and may indicate acquisition of E-selectin ligand expression. These findings provide novel insight into potential adhesive mechanisms promoting hematogenous dissemination of prostate tumor cells into bone.

Topics: Adenocarcinoma; Antigens, Tumor-Associated, Carbohydrate; Bone Marrow Cells; Bone Neoplasms; Cell Adhesion; Cells, Cultured; Disease Progression; E-Selectin; Endothelium, Vascular; Glycoconjugates; Glycoproteins; Glycosphingolipids; Hematopoietic Stem Cells; Humans; Lewis X Antigen; Ligands; Male; Membrane Proteins; Oligosaccharides; Prostate; Prostatic Neoplasms; Sialyl Lewis X Antigen

The prostate specific antigen (PSA) content, the neuroendocrine differentiation and the Lewis(y) and the expression of related carbohydrate antigens in pathological prostatic tissues were determined. These included 13 cancers and 11 benign hyperplasias. PSA is expressed strongly in hyperplastic and poorly in neoplastic tissues. The neuroendocrine differentiation detected by a monoclonal antibody directed against chromogranin A (CgA) is a frequent event in carcinomas and rare in hyperplastic prostate. The Lewis(y) and related carbohydrate antigens, evaluated by the reactivity of the tissues to two monoclonal antibodies MAbB3 and MAbB1, are expressed in a considerable percentage in malignant tissues of prostate and only occasionally in benign lesions. Our results suggest that immunoblotting with antibodies against CgA, B3 and B1 on the tissues, obtained after surgery, may be useful to obtain more information on the neoplastic transformation of human prostate. Furthermore, the expression of Lewis(y) and related carbohydrate antigens on the surface of prostate cancer suggest that, following a clinical trial, an immunotoxin combination of MAbB3 or MAbB1 and Pseudomonas exotoxin, may be used in the treatment of prostate cancer.

Topics: Aged; Antibodies, Monoclonal; Antigens, Tumor-Associated, Carbohydrate; Cell Membrane; Chromogranin A; Chromogranins; Humans; Immunoblotting; Lewis X Antigen; Male; Middle Aged; Neoplasm Staging; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms

Monoclonal antibodies B1 and B3 react with Lewis(y) and related carbohydrate antigens, which are abundant in many solid tumors. These antibodies, when conjugated to a toxin, have been used to target a variety of cancers. Treatment options for advanced prostate cancer are very limited, and there is a need to develop new therapies. In this study, we have asked whether antibodies B1 and B3 react with metastatic lesions from human prostatic carcinoma.. Indirect streptavidin-biotin peroxidase immunohistochemistry was performed on formalin-fixed specimens from prostate cancer metastases. A total of 6 lymph node metastatic samples from patients who did not receive endocrine treatment and specimens of 14 distant metastases from patients who failed hormonal therapy were obtained.. Of the samples, 6 lymph node and 11 distant metastases stained for B1. In the case of B3 staining, 6 lymph node and 10 distant metastatic lesions were positive. In about half of these metastatic samples, more than 40% of cells were immunoreactive with either antibody. Two metastatic samples stained neither for B1 nor for B3 antibody. In general, B1 staining intensity was stronger in samples in which more than 40% of cells were positive.. Our results suggest that B1 and B3 immunoconjugates could be applied to target a substantial percentage of prostate cancer metastases.

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Biotin; Bone Neoplasms; Humans; Immunoconjugates; Immunohistochemistry; Immunotoxins; In Vitro Techniques; Lewis Blood Group Antigens; Lewis X Antigen; Lymphatic Metastasis; Male; Neoplasm Metastasis; Peroxidase; Prostatic Neoplasms; Streptavidin

Alteration of cell surface carbohydrate antigens during malignant transformation is a well-known phenomenon observed in various tumors. In prostatic carcinoma, nearly total deletion of normally occurring ABO and type I-based Lewis antigens, Le(a) and Leb, has been observed in several studies. We studied expression of the closely related type II antigens Le(x), Le(y), and sialyl-Lewis(x) (SLe(x)) using monoclonal antibodies. Thirty formalin-fixed specimens obtained from radical prostatectomy, containing prostatic carcinoma as well as benign tissue, were evaluated by immunohistochemistry. In both cancer and benign tissue, Le(x) expression was minimal or absent. In benign tissue, Le(y) was expressed in ducts and in the basal layer of glandular epithelium. In tumor tissue, Le(y) expression was greatly increased and extensive staining was observed in 26 of 30 cases. The SLe(x) expression in benign tissue was observed only in larger ducts, never in glandular secretory epithelial cells. In carcinoma, rare cells positive for SLe(x) were present in 8 of 30 cases, and stronger expression with focal to patchy distribution was observed in 14 of 30 cases. The results suggest an alteration in glycosyl transferase activity in prostatic carcinoma, with preserved or increased activity of enzymes responsible for the synthesis of the type II core sequence. This sequence is further glycosylated and expressed as the difucosylated compound Le(y) or the monofucosyl, monosialyl compound SLe(x). For prostate, Le(y) and SLe(x) are the only blood group-related antigens known to be minimal or absent in benign secretory epithelial cells that are more highly expressed in malignant tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Biomarkers, Tumor; Humans; Lewis Blood Group Antigens; Lewis X Antigen; Male; Oligosaccharides; Prostatic Neoplasms; Sialyl Lewis X Antigen

Metastatic prostate cancer has an unpredictable long-term prognosis. At present, there are few specific predictors to indicate the outcome for the individual patient. We have studied immunoreactivity for type-2 carbohydrate structures, known to be involved in various cell adhesion processes, in patients with metastatic prostate cancer. One group of patients (n = 26) did not progress within 3 years after orchiectomy, while another group of patients (n = 33) progressed within 1 year following castration and survived less than 2 years. Among the parameters studied, sialyl LewisX carbohydrate up-regulation was the only variable showing significant association with poor prognosis (P < 0.01). Sialyl LewisX discriminated between these two outcome groups with 71% predictability and 96% specificity. Our results indicate that up-regulation of sialyl LewisX is associated with hormonal-resistant, aggressive disease. This prognostic marker may, therefore, have an important role in selecting proper treatment for patients with metastatic prostate cancer.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Carbohydrate Sequence; Humans; Immunohistochemistry; Lewis X Antigen; Male; Middle Aged; Molecular Sequence Data; Neoplasm Metastasis; Oligosaccharides; Predictive Value of Tests; Prognosis; Prostatic Neoplasms; Sialyl Lewis X Antigen; Up-Regulation