Expression Of Tn Research Articles

Aberrant expression of MUC5AC and MUC6 gastric mucins and sialyl Tn antigen in intraepithelial neoplasms of the pancreas

Background & Aims: It has recently been suggested that infiltrating adenocarcinoma of the pancreas arises from histologically well-defined precursor ductal lesions called pancreatic intraepithelial neoplasia (PanIN-1A, -1B, -2, and -3). This study examined alterations in the pattern and the level of expression of several mucin genes (MUC1, MUC2, MUC5AC, and MUC6) and mucin-associated tumor antigens (Nd2 and sialyl Tn) in these precursor lesions. Methods: We examined 139 PanINs and 68 infiltrating ductal adenocarcinomas of the pancreas by using immunohistochemistry and in situ hybridization methods. Results: Overexpression of MUC1, a pan-epithelial mucin, and MUC6, a pyloric-gland mucin, and de novo expression of MUC5AC, a gastric foveolar mucin, was observed in all stages of PanINs and invasive ductal adenocarcinoma. In contrast, the expression of mucin-associated carbohydrate antigen, sialyl Tn, was markedly increased only in PanlN-3 and invasive ductal adenocarcinoma. In addition, a decrease in the expression of these mucin-associated peptide and carbohydrate antigens was correlated with the degree of differentiation of the tumor. Conclusions: Expression of both gastric-foveolar and pyloric-gland mucin in PanINs is an early event, whereas sialyl Tn expression is a late event in the recently defined progression model of pancreatic carcinogenesis. This altered mucin gene expression provides new insight into the role of cell lineage–associated metaplasia in pancreatic carcinogenesis.GASTROENTEROLOGY 2002;123:1052-1060

Carbohydrate antigen expression in primary tumors, metastatic lesions, and serous effusions from patients diagnosed with epithelial ovarian carcinoma: Evidence of up-regulated Tn and Sialyl Tn antigen expression in effusions

The object of this study was the investigation of carbohydrate antigen expression in malignant epithelial cells and benign mesothelial cells in serous effusions from patients diagnosed with epithelial ovarian carcinomas. In addition, to compare antigen expression in carcinoma cells in effusions with those of corresponding primary tumors and metastatic lesions. Sections from 63 malignant effusions from ovarian carcinoma patients and 15 reactive effusions were immunohistochemically stained, using 5 monoclonal antibodies for Lewis y, Sialyl Lewis x, Tn, and Sialyl Tn antigens. Tissue sections ( n = 97) from corresponding primary ovarian carcinomas and metastatic lesions, as well as from 12 malignant mesotheliomas, were additionally stained using the above panel. Staining for the 4 antigens was seen in carcinoma cells in serous effusions in the majority of cases (range = 71% to 85%). In contrast, immunoreactivity was detected in mesothelial cells in only 6% to 23% of the specimens studied ( P < .001 for all 5 markers). With the exception of B3 antibody against Lewis y antigen, malignant mesotheliomas stained negative, infrequently showing focal immunoreactivity. An up-regulation of Tn and Sialyl Tn expression was detected in carcinoma cells in effusions when compared with both primary tumors ( P < .003 and P < .007, respectively) and metastatic lesions ( P < .034 and .041, respectively). Cancer-associated carbohydrate antigens can thus be used as an adjunct in the differentiation between malignant epithelial and reactive mesothelial cells. Ovarian carcinoma cells in effusions show up-regulation of Tn and Sialyl Tn, possibly representing a transient phenotypic alteration facilitating metastasis. H UM P ATHOL 31: 1081-1087.

Simple mucin-type carbohydrate antigens (Tn, sialosyl-Tn, T and sialosyl-T) and gp 230 mucin-like glycoprotein are candidate markers for neoplastic transformation of the human cervix.

Mucins and simple mucin-type carbohydrates are cancer-associated antigens in several human tumors. Expression of Tn, sialosyl-Tn, Thomsen-Friedenreich (T), sialosyl-T and of a recently identified mucin-like glycoprotein (gp230) has not yet been thoroughly investigated in human cervix carcinogenesis. In the present study sections from normal cervix (n=10), CIN III lesions (n=10), and invasive carcinomas (n=47) were evaluated immunohistochemically using monoclonal antibodies. In normal cervix there was: cytoplasmatic expression of Tn in 1 case (10%); membranous expression of STn in 8 cases (80%); no expression of T and cytoplasmatic expression of ST in 1 case (10%); gp 230 was expressed in all cases with a membranous pattern. In CIN III lesions there was cytoplasmatic and membranous expression of Tn in 3 cases (30%) and of STn in 9 cases (90%); T and ST were not expressed; gp 230 was expressed in 5 cases (50%) both in the cytoplasm and at the cell membrane. In invasive carcinomas we observed Tn expression in 30 cases (63.8%) and STn in 31 cases (66%); T antigen was not expressed; expression of both ST and gp 230 in 24 cases (51.1%); all antigens showed membranous and cytoplasmatic staining. Our results show that Tn and ST are good markers of invasive carcinomas of the human cervix. We have also shown that loss of expression of the mucin-like glycoprotein gp 230 is associated with malignant transformation at a preinvasive stage.

Tn antigen is a pre-cancerous biomarker in breast tissue and serum inn-nitrosomethylurea-induced rat mammary carcinogenesis

The Tn determinant (GalNAcalpha-O-Ser/Thr), normally a cryptic structure in mucin-type O-glycans, is a tumor-associated marker which has attracted particular interest in cancer biology. We herein report the characterization of N-nitrosomethylurea (NMU)-induced breast cancer in rats as a new model for the study of aberrant O-glycosylation products. Tn-antigen expression is detectable not only in mammary carcinoma induced by NMU but also in carcinogen-initiated mammary epithelium, indicating that Tn could be a pre-cancerous biomarker in rats treated with NMU. Serum Tn levels were followed up longitudinally in 30 rats from the time of the first injection of NMU to the development of advanced breast cancer. Tn antigen increased in serum several weeks before tumor development, and became highly positive after 56 days of carcinogenesis (prior to breast-cancer occurrence), and the levels correlated with Tn expression in mammary tissues. However, during the follow-up after detection of mammary cancer, all animals displayed a significant decrease of serum Tn antigen, and low levels were observed in animals with advanced breast cancer. We have shown that the humoral immune response to cancer, with the production of anti-Tn antibodies, could hamper the detection of Tn antigen in animals with advanced breast cancer. These results suggest that NMU-induced rat mammary carcinogenesis is a useful experimental model to study the regulation of O-glycosylation at the cellular level during malignant transformation.

Tn antigen is a pre-cancerous biomarker in breast tissue and serum in n-nitrosomethylurea-induced rat mammary carcinogenesis.

The Tn determinant (GalNAcalpha-O-Ser/Thr), normally a cryptic structure in mucin-type O-glycans, is a tumor-associated marker which has attracted particular interest in cancer biology. We herein report the characterization of N-nitrosomethylurea (NMU)-induced breast cancer in rats as a new model for the study of aberrant O-glycosylation products. Tn-antigen expression is detectable not only in mammary carcinoma induced by NMU but also in carcinogen-initiated mammary epithelium, indicating that Tn could be a pre-cancerous biomarker in rats treated with NMU. Serum Tn levels were followed up longitudinally in 30 rats from the time of the first injection of NMU to the development of advanced breast cancer. Tn antigen increased in serum several weeks before tumor development, and became highly positive after 56 days of carcinogenesis (prior to breast-cancer occurrence), and the levels correlated with Tn expression in mammary tissues. However, during the follow-up after detection of mammary cancer, all animals displayed a significant decrease of serum Tn antigen, and low levels were observed in animals with advanced breast cancer. We have shown that the humoral immune response to cancer, with the production of anti-Tn antibodies, could hamper the detection of Tn antigen in animals with advanced breast cancer. These results suggest that NMU-induced rat mammary carcinogenesis is a useful experimental model to study the regulation of O-glycosylation at the cellular level during malignant transformation.

Expression of Carbohydrate Antigens in Advanced-Stage Ovarian Carcinomas and Their Metastases—A Clinicopathologic Study

Objective. Up-regulated expression or loss of expression of various carbohydrate antigens on the surface of cancer cells has been associated with a metastatic phenotype and poor survival in epithelial malignancies of different origins. The object of this study was to investigate the expression of carbohydrate antigens in two groups of patients diagnosed with advanced-stage ovarian carcinoma—one with an extremely favorable outcome and the other with a uniformly poor survival.Methods. Sections from 76 paraffin-embedded blocks (primary ovarian carcinomas and metastatic lesions) from 45 patients diagnosed with advanced-stage ovarian carcinomas (FIGO stages III–IV) were immunohistochemically stained using five monoclonal antibodies for Lewisy (Ley)(two antibodies), Sialyl Lewisx (Slex), Tn, and Sialyl Tn (STn) antigens. Patients were divided in two groups based on outcome. Long-term survivors (21 patients) and short-term survivors (24 patients) were defined using a double cut-off of 36 months for disease-free survival (DFS) and 60 months for overall survival (OS). Staining results for primary tumors and metastases were analyzed separately.Results. Mean follow-up period was 70 months. The mean values for DFS and OS were 109 and 125 months for long-term survivors and 3 and 25 months for short-term survivors. Staining for all four antigens was seen in the majority of cases (range = 72–96%) and tended to be comparable in primary tumors and their metastases. However, absence of immunoreactivity for STn was seen in 9/38 (24%) metastatic lesions and only 1/38 (3%) primary tumors. This finding did not reach statistical significance (P > 0.05). A combined pattern of membranous and cytoplasmic staining was predominant in the majority of cases. Enhanced staining for Ley and STn was detected in the invasive front of some tumors, while Slex and Tn immunoreactivity did not relate to cell location. Primary tumors and metastatic lesions of long-term survivors displayed immunoreactivity patterns that were comparable to those of short-term survivors. In the evaluation of survival curves, more diffuse staining for Slex showed marginal correlation with poor survival (P = 0.05), while a trend toward poorer survival was seen in tumors that were more extensively stained for Ley and Tn (P > 0.05).Conclusions. Ley, Slex, STn, and Tn antigens are widely expressed in primary ovarian carcinomas and their metastases. Altered expression of Sialyl Tn is observed with tumor progression in a fraction of ovarian carcinomas. Expression of membrane carbohydrate residues is prevalent in tumors of both long-term and short-term survivors and does not appear to be a strong predictor of disease outcome. However, larger studies are needed to further elucidate the role of these molecules in ovarian carcinogenesis.

Clinicopathologic and Prognostic Significance of the Expression of Mucins, Simple Mucin Antigens and Histo-Blood Group Antigens in Papillary Thyroid Carcinoma.

We have previously analyzed the expression of MUC1, underglycosylated MUC1, MUC2, MUC5AC, Tn, sialyl Tn, Lewis(a), sialyl Lewis(a), Lewis(x), and sialyl Lewis(x) in papillary thyroid carcinoma (PTC). The present study of 26 thoroughly scrutinized cases of PTC with "good" or "bad outcome" and a minimum of 10 yr of follow-up (or until death of the patients) was undertaken in an attempt to find if there is any relationship between the expression of the aforementioned antigens and the clinicopathologic and morphologic features of the cases and to evaluate the prognostic significance of the immunohistochemical pattern of PTC. We observed a significant or suggestive association between the expression of MUC1, underglycosylated MUC1, MUC2, Lewis(a), and Lewis(x) and the older age of the patients, and a suggestive association between Lewis(x) expression and lymph node metastasis and venous invasion. There was also a strong correlation between extrathyroid invasion, lymph node metastasis, intrathyroid dissemination, and venous invasion and patients outcome thus demonstrating, once more, the prominence of the classic clinicopathologic and morphologic features in the prognostic evaluation of PTC. The immunohistochemical study of mucins, simple mucin antigens, and histo-blood group antigens did not provide additional prognostic information, but for the significant association of Lewis(x) immunoreactivity to the group of "bad outcome."

Prognostic Relevance of Tn Expression in Breast Cancer.

BACKGROUND: Abnormal glycosylation patterns have been recognized as a featureof carcinomaassociated mucins. The expression of the Tn antigen in breast cancer tissue was investigated to assess its prognostic relevance. METHODS: Formalin-fixed, paraffin-embedded materials from 219 patients with breast cancer were used. Immunohistochemical staining of the Tn antigen was retrospectively investigated and a lesion staining 10% or more was considered positive RESULTS: Tn antigen expression was present in 99 (45%) of 219 lesions. There were no correlations between Tn antigen expression and mean patient age, nodal status, estrogen receptor status, or menopausal status, but there was a slightly significant association between Tn and tumor size. Patients negative for the Tn antigen had a significantly better survival rate than those who were positive. Multivariate analysis also indicated that Tn expression correlated significantly with overall survival in addition to nodal status and tumor size. CONCLUSION: Tn expression was a significant prognostic factor in breast cancer, but the significance was lost on multivariate analysis. The biological implication of Tn expression in breast cancer needs further investigation.

Regular albuterol or nedocromil sodium — effects on airway subepithelial tenascin in asthma

Both albuterol and nedocromil sodium have been recognized to possess certain anti-inflammatory properties. However, there are no data on the impact of these drugs on the pathophysiology of the bronchial extracellular matrix in asthma characterized by enhanced tenascin (Tn) expression, known to occur proportional to the severity of asthma. This paper reports data from a morphometric study on the effects of regular treatment with inhaled albuterol or nedocromil sodium on the extent of bronchial subepithelial deposition of Tn, collagen types III, IV, and VII and mucosal infiltration with macrophages. Thirty-two patients (14 women) with chronic asthma, aged 38·7 years (median) with a median forced expiratory volume in 1 sec (FEV 1) of 74·4% predicted, were selected to undergo fibre-optic bronchoscopy with bronchial biopsies before and after 12 weeks of treatment with either inhaled albuterol 0·2 mg or nedocromil sodium 4 mg four times daily according to a double-blind protocol. Cryostat sections of the biopsy specimens were studied by indirect immunostaining techniques using monoclonal antibodies and computer-assisted quantitative image analysis. Albuterol treatment significantly reduced the median thickness of subepithelial Tn expression from 9·7 to 6·3 μm ( P=0·023) and macrophage numbers in the epithelium ( P=0·034), lamina propria ( P=0·039) and entire mucosa ( P=0·033), whereas nedocromil sodium had no effect. Expression of the collagen types was not affected by either treatment. There was no identifiable statistical difference between the two treatments for any of the outcome variables measured. Nevertheless, the results demonstrate that even a short-acting β 2-agonist may exert anti-inflammatory potential sufficient to interfere with the basic mechanisms of asthma as shown by reduction of subepithelial Tn content and mucosal macrophage count.

Different expression of Tn and sialyl-Tn antigens between normal and diseased human gastric epithelial cells.

Thomsen-Friedenreich antigen (T antigen) has been supposed to be a cancer-specific carbohydrate antigen. We have previously shown that one third of the Japanese population normally expressed T antigen in gastric surface epithelia and the other two thirds expressed fucosyl-T antigen. Their sialylation and blocked-synthesis were associated with diseased conditions. In the present study, we studied gastric surface epithelial expression of monosaccharide antigen Tn, i.e., a precursor of T antigen, and sialyl-Tn. Normal fundic and pyloric epithelia, respectively, expressed Tn supranucleally and cytoplasmically, but did not express sialyl-Tn. In the intestinal metaplasias and intestinal-type adenomas, goblet cells expressed sialyl-Tn in their vacuoles, and absorptive cells expressed Tn apically. In gastric-type adenomas, Tn, but not sialyl-Tn, was detected. Intestinal-type cancers expressed Tn and sialyl-Tn more often than the diffuse-type cancers. Five cancers did not express Tn, sialyl-Tn, or the T-related antigens. In these, four were diffuse-type cancers. We concluded that: a) normal gastric epithelial cells express Tn; b) metaplastic differentiation is associated with sialylation of Tn and c) expression of Tn and sialyl-Tn is depressed in the gastric cancers.

Glycopathological study of eyelid tumors and pseudotumors

The expression of MUC1, Tn (GalNAc α 1-O-Ser/Thr) and sialosyl Tn (STn) (NeuAc α 2,6 GalNAc α 1-O-Ser/Thr) antigens, which are useful markers for the prognosis of cancer in other organs, was examined immunohistochemically in a series of 45 eyelid tumors and 5 pseudotumors: basal cell carcinoma, 18; squamous cell carcinoma, 11; sebaceous gland carcinoma, 6; seborrheic keratosis, 4; papilloma, 3; verruca vulgaris, 2; nevus, 1; and granuloma, 5. The MUC1 antigen was identified in all squamous cell and sebaceous gland carcinomas, but not in basal cell carcinoma or the benign tumors. The Tn antigen was expressed in all the sebaceous gland, half of the squamous cell, and only rarely in the basal cell carcinomas. The STn antigen was expressed in all seborrheic keratosis and in the majority of squamous cell carcinomas, but only rarely in sebaceous gland and basal cell carcinomas. Eyelid tumors are frequently associated with apomucin and mucin-carbohydrate antigens: the MUC1 glycoprotein appears to be related to the malignant potential of eyelid tumors, and may be a useful marker for the differential diagnosis of invasive tumors, including sebaceous gland and squamous cell carcinomas.

Mucin carbohydrate antigens (T, Tn, and Sialyl-Tn) in human ovarian carcinomas: Relationship with histopathology and prognosis

Altered glycosylation of mucins leading to the expression of T, Tn, and sialyl-Tn antigens has been shown in ovarian carcinoma, but its relationship with prognosis is still unclear. We investigated immunohistochemically the expression of these antigens in 38 (17 serous and 21 mucinous) ovarian carcinomas to assess their potential prognostic value as compared with stage of disease, histopathology of tumors, and survival time of patients. Eight benign ovarian tumors (four serous and four mucinous), and four normal ovarian tissues also were studied. Of the 38 carcinomas, 25 (66%) expressed T, 27 (71%) expressed Tn, and 33 (87%) expressed sialyl-Tn antigens. Most cases (83%) expressed two or all of the three types of antigens simultaneously. Normal ovarian epithelia showed no staining for these antigens, and benign ovarian tumors were either negative or occasionally expressed weak staining in less than 25% of epithelial cell areas. Statistical analyses showed strong associations between Tn and sialyl Tn antigen expressions and disease stage as well as histological grade. In 19 ovarian carcinoma patients with available survival data, the overall survival times of patients with high Tn or sialyl-Tn antigen expression were significantly worse than those of the patients with negative and low expression ( P < .05 and P < .01). In multivariate stepwise regression analysis, disease stage ( P = .000) and Tn antigen expression ( P = .02) were found to be significant independent parameters associated with the overall survival time. These findings suggest that, with exception of T antigen expression, the expression of Tn and sialyl-Tn antigens in ovarian carcinomas may provide additional prognostic information on patient outcome.

Molecular cloning of a monoclonal anti-tumor antibody specific for the Tn antigen and expression of an active single-chain Fv fragment.

We report here the first amino acid sequence of an anti-Tn monoclonal antibody raised against human breast cancer cells and show that a single chain Fv fragment of this IgM retains the Tn-binding specificity as defined by functional assays with asialo-OSM and membrane extracts from MCF-7 cells. Sequence comparisons and molecular modeling of 83D4 indicate that the antibody combining site displays a cavity-like feature primarily defined by the CDR H1 and H2 loops. This pocket could accommodate a single Tn molecule, thus, suggesting a structural explanation for the predominant expression of a particular VH gene segment in a group of antibodies that recognize tumor-associated antigens arising from an aberrant O-glycosylation.

The expression of tenascin and fibronectin in keratoconus, scarred and normal human cornea.

The etiology and pathogenesis of keratoconus remain unclear, and therefore we decided to study the distribution of different isoforms of tenascin (Tn) and fibronectin (Fn) in normal human corneas and in those obtained from penetrating keratoplasty for keratoconus and corneal scarring. Frozen sections of human cornea and conjunctiva were stained by immunohistochemical methods with a panel of monoclonal antibodies (MAbs) against different isoforms of Tn and Fn. In the normal human eye, Tn was found in the limbal and conjunctival basement membrane region, in the conjunctival blood vessels and at the junction of the cornea and sclera, but no immunoreaction was seen in the normal cornea. In the corneas from the keratoconus patients, a clear immunoreaction for Tn was seen in the defects of Bowman's membrane as well as in the distorted stroma beneath the defects. In some of the keratoconus corneas, basement membrane adjacent to the defects also showed reactivity for Tn, and in clinically and histologically scarred keratoconus corneas the scars expressed Tn. In the scarred corneas, only blood vessels in the posterior portion of the cornea showed immunoreactivity for Tn, while no Tn was noted in the scar area or in Bowman's membrane. No major differences were noticed in the reactivity of different MAbs against Tn isoforms. Fn, extradomain A Fn (EDA-Fn) and oncofetal Fn (onc-Fn) were found in the basement membrane of the central cornea of the normal eye. In keratoconus corneas, the defects and clinical and histological scars bound MAbs against Fn, EDA-Fn and onc-Fn, but in the scarred corneas no enhancement in the expression of Fns was noted. Extradomain B cellular Fn (EDB-Fn) was not expressed in any of the eyes studied. The results suggest that the anterior portion of the cornea is involved in the pathogenesis of keratoconus. Furthermore, it seems that the expression of Tn and Fns in the clinically scarred keratoconus corneas is due to a process in which both repairing and scar-forming mechanisms operate at the same time. However, the origin of the defects in Bowman's membrane seen in keratoconus still remains unclear. They may be minor scars due to the disease or primary defects in the process leading to keratoconus.

Expression of tenascin in invasion border of early breast cancer correlates with higher risk of distant metastasis.

Tenascin (Tn) is an extracellular matrix glycoprotein transiently expressed in epithelial-mesenchymal interaction areas during embryogenesis. Tn is expressed in a limited manner in adult tissues but emerges during wound healing and tumorigenesis. We have studied Tn expression by immunohistochemistry in 137 small node-negative breast cancers treated with breast-conserving surgery and post-operative radiotherapy during 1985-1989. None of the patients had undergone any adjuvant hormonal therapy or chemotherapy. Stromal Tn expression itself could not predict distant metastasis. However, Tn staining in the area of the invasion border seemed to be a strong predictor of distant metastasis, with an estimated 5-year metastasis-free survival (MFS) of 85% in Tn-positive cases compared to 98% in Tn-negative ones. The prognostic impact of Tn in the invasion border on MFS was stronger than that of tumour size and grade. This staining appears to be a useful adjunct for the estimation of breast-cancer metastasis.

Expression of Simple Mucin Type Antigens and Lewis Type 1 and Type 2 Chain Antigens in the Thyroid Gland: An Immunohistochemical Study of Normal Thyroid Tissues, Benign Lesions, and Malignant Tumors.

In order to characterize the pattern of expression of carbohydrate structures in several types of thyroid tissues and to evaluate the putative usefulness of the detection of such antigens in diagnostic surgical pathology, we undertook the immunohistochemical study of simple mucin type antigens (T, Tn, and sialyl Tn), Lewis type I antigens (Lewis a, sialyl Lewis a, and Lewis b), and Lewis type 2 related antigens (precursor type 2, H type 2, Lewis x, sialyl Lewis x, and Lewis y) in thyroid samples obtained from 65 patients. The material consisted on paraffin sections of normal thyroid (n = 43), benign lesions (13 goiters/hyperplastic lesions and 15 adenomas), and malignant tumors (12 follicular carcinomas and 27 papillary carcinomas, 5 of which had lymph node metastases) of the thyroid follicular epithelium. Tn, T, and precursor type 2 antigens were the only antigens that were detected and very rarely in normal thyroid. Benign lesions were similar to normal thyroid despite displaying a higher prevalence of immunoreactivity for several antigens of the three groups. Thyroid carcinomas presented a significantly higher level of expression of all types of simple mucin, Lewis type 1, and Lewis type 2 antigens than the normal thyroid and benign lesions. The expression of sialyl Tn was restricted to malignant tumors, and the expression of sialyl Lewis x was closely associated, though not exclusively, to papillary carcinomas. The immunoreactivity was stronger and the number of positive cases was higher in papillary than in follicular carcinomas. No differences were found between primary tumors and the respective metastases. The existence of distinct patterns of expression of carbohydrate antigens in different types of thyroid lesions points to the usefulness of the detection of some of these antigens in thyroid surgical pathology. The putative role of such antigens in the peculiar metastatic properties of thyroid carcinomas remains unsettled.

Immunohistochemical expression of Sialyl Tn, Sialyl Lewisa, Sialyl Lewisab, and Sialyl Lewisx in primary tumor and metastatic lymph nodes in human gastric cancer

Sialyl Lewis Tn(STN), Sialyl Lewisa(CA19-9), Sialyl Lewisa−b−(DU-PAN-2), and Sialyl Lewisx(SLX) antigens were immunohistochemically examined in the primary tumor and metastatic lymph nodes in 35 patients with advanced gastric cancer. STN, CA 19-9, DU-PAN-2, and SLX were expressed in 91%, 60%, 31%, and 60% in the primary lesion, and 77%, 54%, 22%, and 51% in the metastatic lesion, respectively. In only four cases, (11%) were all four antigens expressed in both the primary and metastatic lesions. Three antigens were expressed in 49% of primary lesions and in 20% of metastatic lesions. Compared with expression in primary lesions, increased, unchanged and decreased expressions in metastatic lesions were noted in 23%, 37%, and 40% for STN, 20%, 40%, and 40% for CA19-9, 17%, 57%, and 26% for DU-PAN-2, and 26%, 31%, and 43% for SLX, respectively. These results indicate that the tumor in the primary and metastatic lesions has a heterogeneous expression of sialyl-related antigens. However, metastases cannot be predicted based upon the expression of these antigens. © 1996 Wiley-Liss, Inc.

Flow cytometric analysis of T and Tn epitopes on chronic lymphocytic leukemia cells

Immunophenotyping of peripheral blood lymphocytes from six patients with B-cell chronic lymphocytic leukemia (B-CLL) and five normal volunteers was done and their T and Tn epitopes analyzed using specific monoclonal antibodies and flow cytometry. Lymphocytes from all patients showed strong Tn expression as compared to normal control lymphocytes. By contrast, T antigen was not expressed. The Tn expression may be a useful diagnostic and prognostic marker for B-CLL. © 1996 Wiley-Liss, Inc.

Expression of Mucin Carbohydrate Antigens (T, Tn and Sialyl Tn) and MUC-1 Gene Product in Intraductal Papillary-Mucinous Neoplasm of the Pancreas

Aberrant or incomplete glycosylation of mucins results in expression of T, Tn, and sialyl-Tn (STn) antigens in various malignant neoplasms. MUC-1 gene product (a mucin core protein of mammary type) is known to alter or overexpress in several malignant tumors. However, expression of these mucin-related antigens has rarely been examined in intraductal papillary-mucinous neoplasm (IPN) of the pancreas. The authors examined immunohistochemically the expression of these antigens and MUC-1 gene product in nine IPN. In normal pancreas (n = 5), pancreatic ducts did not express T, Tn, or STn antigens, but expressed MUC-1 gene product. Among the nine IPNs, two (22%) expressed T antigen, nine (100%) expressed Tn antigen, and seven (78%) expressed STn antigen. MUC-1 gene product was expressed in nine (100%) IPNs. In invasive ductal adenocarcinoma of the pancreas (n = 6), all cases showed strong expression of Tn and STn antigens and the MUC-1 gene product, but expressed no T antigen. The expression of these antigens and MUC-1 gene product was focal in IPN, whereas it was diffuse in invasive ductal adenocarcinoma of the pancreas. These data suggest that aberrant or incomplete glycosylation occurs in epithelial mucins of IPN, that IPN is a borderline or low grade malignant neoplasm in terms of mucin-related antigen expression, and that mucin core protein (MUC-1 gene product) does not alter during pancreatic ductal carcinogenesis.

Tn and sialyl-Tn antigens as potential prognostic markers in human ovarian carcinoma.

Carcinoma-associated Tn and sialyl-Tn antigens have been shown to aid in the prediction of tumor aggressiveness. The purpose of this study was to evaluate the prognostic value of Tn and sialyl-Tn antigen expression in human ovarian carcinoma. Formalin-fixed, paraffin-embedded tissue sections from 32 primary ovarian carcinomas, 6 benign and 2 normal ovarian tissues were immunostained using monoclonal antibodies against Tn and sialyl-Tn antigens and a streptavidin-biotin-peroxidase method Immunostainings were assessed semiquantitatively and the measurements were then correlated with the established prognostic factors of ovarian carcinoma. i.e. disease stage and histological grade. Of the 32 ovarian carcinomas, 22 (69%) expressed Tn and 28 (87.5%) sialyl-Tn antigens. Immunostaining measures for Tn antigen were significantly associated with the clinical stage (p < or = 0.02) and histological grade (p < or = 0.05) of the tumors. The results for sialyl-Tn antigen revealed more significant associations with the clinical stage (p < or = 0.002) and histological grade (p < or = 0.007). The clinical stage and histologic grade of the tumors were also highly correlated with each other. Similarly, combined Tn and sialyl-Tn antigen expression revealed significant correlations with the prognostic factors. Benign and normal ovarian tissues showed no reactive Tn and sialyl-Tn antigen. The extent of Tn and sialyl-Tn antigen expression in primary ovarian carcinoma may contribute to the prognosis of the disease.