Expression of sialyl-Tn, Tn and T antigens in primary liver cancer

Sialyl-Tn, Tn and T antigens are caused by aberrant or incomplete glycosylation of apomucins and are related to the aggressiveness of malignant neoplasms. Using 41 liver samples from patients with cholangiocarcinoma (including four with cirrhosis), 21 with combined hepatocellular-cholangiocellular carcinoma and 17 with hepatocellular carcinoma, the expression of sialyl-Tn, Tn and T antigens were characterized immunohistochemically and the correlation with apomucin profiles was evaluated. The prevalence of sialyl-Tn, Tn and T antigens expression was 89, 95 and 51% in cholangiocarcinoma without cirrhosis; 25, 75, and 0% in cholangiocarcinoma with cirrhosis; 29, 90, and 48% in combined hepatocellular-cholangiocellular carcinoma; and 0, 12 and 6% in hepatocellular carcinoma, respectively. Sialyl-Tn antigen was frequently expressed in cholangiocarcinoma without cirrhosis compared with cholangiocarcinoma with cirrhosis and combined hepatocellular-cholangiocellular carcinoma (P < 0.01). Although sialyl-Tn expression was associated with MUC1, MUC6 and MUC7 expression, the expression sites among them were not identical in the individual cases. These data suggest that the different expressions of sialyl-Tn antigen among cholangiocarcinoma without cirrhosis, cholangiocarcinoma with cirrhosis and combined hepatocellular-cholangiocellular carcinoma may reflect the biological features inherent to these tumors, such as the ability of invasion.     

The immunoexpression of Tn, sialyl-Tn and T antigens in chronic active gastritis in relation to Helicobacter pylori infection

The simple mucin-type carbohydrate antigens Tn, sialyl-Tn and T represent the mucin core oligosaccharide structures that are produced in the initial steps of mucin biosynthetic pathway. Utilising monoclonal antibodies anti-Tn antigen, anti-sialyl-Tn antigen and anti-T antigen, we have investigated the expression of the simple mucin-type carbohydrate antigens in 47 biopsy specimens of antral mucosa with chronic active gastritis, 25 of which had Helicobacter pylori infection. The Tn immunoreactivity, localised at the supranuclear region of surface and glandular mucous cells, was observed in all samples, independently from H. pylori status. The sialyl-Tn antigen, mainly localised in the cytoplasm of glandular mucous cells and in goblet cells vacuoles, was seen in 56% of the cases with H. pylori infection and in 41% of the cases in the H. pylori-negative group. In addition, the T antigen was found in the cytoplasm of surface and glandular mucous cells in 16% of the H. pylori-positive group, whereas the percentage of positive cases was reduced to 5% in H. pylori-negative patients, with an exclusive localisation in the cytoplasm of glandular mucous cells; after neuraminidase treatment, the percentage of T antigen-positive cases was increased to 28% in H. pylori-positive cases and to 27% in negative cases. No significant relationships between H. pylori infection and Tn, sialyl-Tn or T antigen immunoexpression were encountered in our cases. Therefore, we maintain that the inflammatory infiltrate may itself play an important role in the expression of simple mucin-type carbohydrate antigens in chronic active antral gastritis.     

Immunodetection of sialyl-Tn antigen in normal,hyperplastic and cancerous tissues of the uterine endometrium

Summary The expression of sialyl-Tn antigen (STn) in normal, hyperplastic and neoplastic tissues of the uterine endometrium was examined by immunoperoxidase staining of formalin-fixed, paraffin-embedded samples using the monoclonal antibody TKH-2, directed toward the STn structure (NeuAc 2–6GalNac 1-O-serine or threonine). STn was expressed in 13 of 18 normal postovulatory endometria with an increasing staining intensity and incidence in the late secretory phase. It was consistently absent in 10 proliferative endometria. None of 5 cystic, 4 adenomatous or 12 atypical hyperplasias expressed STn, but areas of severe cytological atypia in 3 atypical hyperplasias showed faint expression. STn expression was detected in 36 of 43 adenocarcinomas. Although the extent of staining varied from a few to most of the cancer cells, general staining was observed throughout the cytoplasm of cancer cells with increased staining of the luminal surface and frequent positive staining of intraluminal mucin. Thus, it is clear that STn is selectively expressed in cancer cells and shows restricted expression in normal and hyperplastic endometrial tissues. STn may be an early marker of malignant transformation and has potential for use as a diagnostic aid in the surgical pathology of the uterine endometrium.     

T-Synthase活性对胃癌Tn/STn及T/ST抗原表达的影响

胞;Tn+细胞同时表达Tn/STn抗原,不表达T/ST抗原,Tn-Ⅰ及Tn-细胞均表达ST抗原,部分Tn-Ⅰ细胞可见T抗原表达;Tn+、Tn-Ⅰ及Tn-细胞间T-Synthase mRNA无明显差别,T-Synthase活性在Tn+细胞明显下降.结论 不同TNM期胃癌组织中Tn、STn、T、ST抗原表达存在差异,T-Synthase活性降低可能导致胃癌细胞表达Tn抗原.     

The expression of Tn and S-Tn antigens in cancer and pre-malignant lesion of colorectal tissues by enzyme immunohistochemical method

Expression of Tn and S-Tn antigens was examined by enzyme immunohistochemical SABC method in cancer, adenoma, hyperplastic polyps, normal adult and fetal colorectal tissues. Both antigens were proved to be oncofetal colorectal cancer-associated. S-Tn was considered to be the better marker, which give no expression in normal adult colorectal tissues, but does express in 81.3% of the cancer tissues, as well as in adenoma. S-Tn increased parallelly with the development of malignant potential changes, such as increasing of size, degree of dysplasia, and increase of villous histological patterns. Experimental data also demonstrated that in colonic cancer cells, a special sialic acid transferase, which is not existent in normal adult colon epithelium, partly changes Tn antigen to S-Tn; thus, T, Tn, and S-Tn antigens are possible to be coexistent in colorectal carcinoma.     

Distribution of sialosyl Tn and Tn antigens within normal and malignant colorectal epithelium

Expression of the core blood group structures sialosyl Tn (STn) and Tn is regarded as a colorectal cancer-specific change reflecting truncated synthesis of the oligosaccharide component of goblet cell mucin. The distribution of STn and Tn in normal and malignant epithelium has been studied in detail by a combination of mucin-, lectin-, and immunohistochemistry with and without pretreatment with potassium hydroxide (KOH), neuraminidase, and KOH–neuraminidase. When O-acetylated sialic acid (neuraminidase-resistant) is converted by saponification to non-O-acetylated sialic acid (neuraminidase-sensitive), normal colorectal goblet cells (mainly of the lower two-thirds of crypts) are immunoreactive with the monoclonal antibody TKH2 (specific for STn). This immunoreactivity is abolished by the interposition of neuraminidase, but goblet cells then become immunoreactive with Hb-Tn1 (specific for Tn). While colorectal cancer mucin expresses STn, expression of Tn is not seen in either goblet cell mucin or extracellular material showing the morphological and histochemical characteristics of secretory mucin. Tn expression in cancers is mainly limited to the Golgi zone and in a proportion of cases to cytoplasm and apical membrane (glycocalyx) of columnar cells and inspissated material within lumina. The material reacting with Hb-Tn1 may be upregulated, membrane-associated MUC1 glycoprotein rather than MUC2 or MUC4 goblet cell mucin. The presence of STn and cryptic Tn within normal colorectal goblet cells and the absence of Tn expression within colorectal cancer secretory mucin contradicts the generally accepted concept of cancer-specific incomplete glycoprotein synthesis within these neoplasms.     

Protein tumor antigens.

Immunogenic tumor antigens have been sought through a variety of paradigms for several past decades. Recent developments in antigen presentation have radically changed the prism through which we view these enigmatic antigens. This article discusses the small but growing treasure chest of these antigens--stress-induced proteins, the P1AB antigen of the P815 mastocytoma, the p53 tumor suppressor protein, the gp95/p97 antigen of human melanoma, mucins and others.     

OY-TES-1在肿瘤组织中的表达及生物信息学分析

目的:了解OY-TES-1mRNA及其蛋白在肿瘤组织中的表达情况,初步探讨其结构与功能.方法:利用定量PCR和免疫组织化学技术检测肿瘤组织中OY-TES-1的表达,结合生物信息学技术分析其结构和功能.结果:肿瘤与瘤旁组织中目的基因mRNA的表达频率分别为61.95%和59.57%,其中肝细胞癌72.97%、脑膜瘤55.56%、胶质瘤57.50%,肿瘤组织中该基因mRNA的表达量明显高于瘤旁组织.目的蛋白在胃癌的阳性率为25.00%,肝细胞癌40.00%,结肠癌46.67%,而瘤旁组织与肺癌均为阴性反应.生物信息学分析提示目的蛋白富含螺旋结构,具有一个信号肽、多种修饰位点及sp32结构域,存在较多T、 B细胞表位且主要位于目的蛋白的羧基端.结论:OY-TES-1mRNA及其蛋白均可在肿瘤组织中表达,生物信息学分析结果提示该蛋白功能的多样性.     

Expression of blood group antigens by normal bronchopulmonary tissues and common forms of pulmonary carcinomas.

The expression of ABH and Lewis antigens has been studied in a series of pulmonary carcinomas, in areas of squamous metaplasia, and in normal adjacent bronchopulmonary tissues by means of a panel of lectins and monoclonal antibodies. All respiratory epithelial cells can express antigens, with the exception of glandular serous cells. The expression of AB antigens is rather homogeneous, while Lewis antigens are expressed in a more irregular pattern, alternating positively stained cells with negatively stained cells in the same microscopic field. The expression of blood group antigens allows the identification of residual pneumocytes inside the tumor and the proper classification of some neoplasms. Metaplastic areas show a variation in the staining profile when compared with normal tissues and pulmonary carcinomas. The most significant findings are the deletion of A antigen and the strong expression of Le antigen. Pulmonary carcinomas are composed by a heterogeneous population and tend to express antigens in the more differentiated cases or areas. The most important findings are the deletion of AB antigens and the strong expression of Le(y) antigen.     

胃癌组织HLA－I类和DR分子免疫组化研究

本文应用免疫组化法对６４例胃癌、癌旁组织和６例胃溃疡大致正常胃粘膜冰冻和石蜡切片进行了染色．结果表明，正常胃粘膜和癌旁胃粘膜上皮细胞ＨＬＡ－Ｉ类分子表达阳性，其着色较均一，ＨＬＡ－ＤＲ染色均阴性．胃癌细胞Ｉ类分子表达缺失（２７／６４例），与癌旁上皮比较差异显著（Ｐ＜０．０１）。粘液细胞癌和低分化癌Ｉ类分子缺失率显著高于高分化癌（Ｐ＜０．０２５）．此外，发生肿瘤转移的病例Ｉ类分子缺失率（１２／１５例）显著高于无转移组（１／５例，Ｐ＜０．０２５）．ＤＲ分子在癌组织表达阳性，其阳性率高达５３．１％（３４／６４例）．低分化癌ＤＲ分子阳性率亦显著高于高分化癌和中分化癌，未分化癌ＤＲ分子阳性率亦显著高于高分化癌（Ｐ＜０．０１～０．０５）．提示（１）ＨＬＡ－Ｉ类分子表达缺失可能与癌细胞逃避宿主免疫监视发生润浸生长和转移有关；（２）分化程度不同的癌组织ＨＬＡ－Ｉ类分子表达差异显著，提示癌细胞分化可能影响Ｉ、Ⅱ类分子表达和肿癌抗原呈递；（３）ＨＬＡ－Ｉ类和ＤＲ分子表达异常可能是上皮恶性转变的标志之一．     

Calcitonin secreting struma-carcinoid tumor of the ovary.

The ultrastructure of strumal carcinoid tumors at times may reveal a far more complex structure than can be ascertained from light microscopy. It may at times be indistinguishable from medullary carcinoma of the thyroid gland. Both tumors appear to be capable of producing 5-hydroxyindolacetic acid and calcitonin. The common shared biologic and ultrastructural features suggest a common origin, from neuroectodermal cells.     

Collision tumor: serous adenocarcinoma and steroid cell tumor of the ovary.

A "collision" tumor between a serous papillary adenocarcinoma and a steroid cell tumor of the ovary is described. No similar combination has been reported in the literature. The steroid cell component secreted testosterone, resulted in considerable virilization of the patient, and appears to have preceded the carcinoma by several years. It remains problematical whether the androgenic milieu may have predisposed to the development of the second, malignant, tumor.     

Expression of native and deglycosylated colon cancer mucin antigens in normal and malignant epithelial tissues

Immunohistochemical techniques were used to determine the distribution and cellular location of the mature and precursor forms of a colonic-type mucin in normal and malignant epithelial tissues. The antisera used in this study were prepared against native human colon cancer mucin (LS), partially deglycosylated mucin (HFA or GalNAc-apomucin), and fully deglycosylated mucin (HFB or apomucin). These antisera reacted with most mucin-producing cells of the normal gastrointestinal tract, salivary ductular cells, bronchial epithelial cells, some bronchial mucous glands, and squamous epithelial cells of the esophagus. Breast, endometrium, ovary, prostate, liver, and thyroid were nonreactive. In most normal organs, HFB reactivity was present in the supranuclear and perinuclear cytoplasm and LS and HFA were located primarily in goblet cell vacuoles, apical cytoplasm, and luminal secretions. These findings are consistent with the expected subcellular locations of apomucin and more "mature" mucins. LS, HFA, and HFB were frequently expressed in adenocarcinomas of the colon, stomach, pancreas, and lung. Lymphoma, sarcoma, and melanoma specimens were nonreactive. Alterations in the expression of these mucin antigens in malignant tissues included loss of subcellular compartmentalization, increased intensity of staining, and disappearance of staining. In addition, de novo expression of HFB was observed in one of five breast carcinomas and three of five ovarian mucinous cystadenocarcinomas. These data demonstrate that LS, HFA, and HFB are useful for studying the organ specificities and biosynthetic pathways of one type of mucin in normal and malignant tissues.     

肿瘤易感基因101在肝细胞肝癌组织中的表达及意义

目的:检测TSG101(TSG101)在肝细胞肝癌(HCC)组织中表达的临床意义。方法:应用免疫组织化学及Westernblot方法检测TSG101蛋白在肝癌及其对应非癌肝组织组织的表达情况,并分析其在肿瘤中表达水平与患者年龄、性别、TNM分期及转移等临床病理资料之间的关系。结果:免疫组化及Western blot均显示TSG101在肝癌组织表达水平显著高于其对应非癌肝组织(P<0.05)。TSG101高表达与患者TNM分期及侵袭转移显著相关(P<0.05),而与患者性别、年龄及血清HBsAg水平无明显相关性(P>0.05)。多因素回归分析同样提示TSG101阳性表达率与患者TNM分期及转移相关(P<0.05)。结论:TSG101在肝细胞癌表达水平显著高于其对应非癌肝组织,其在肝癌表达水平与患者TNM分期及转移密切相关。     

Detection of cytomegalovirus antigens and DNA in tissues fixed in formaldehyde.

Immunohistochemical techniques with monoclonal antibodies against cytomegalovirus (CMV) immediate early (IEA) and early antigens (EA), and in situ hybridisation, were used to detect CMV infection in routinely obtained, formaldehyde fixed and paraffin wax embedded tissues taken from bone marrow transplant patients, who had died form interstitial pneumonia. To improve the rates of detection of CMV-IEA and EA the wax embedded material was pretreated with 0.4% pepsin/HCl at 37 degrees C for 30 minutes. This pretreatment was also advantageous for in situ hybridisation. In the patients with histological evidence of CMV infection or positive viral culture from the lung tissue, or both, viral proteins and nucleic acids were detected in lung, as well as in other organs. Immunohistochemical techniques proved superior in heavily infected but necrotic tissues. In control patients (patients who had died from interstitial pneumonia without any evidence of CMV, or with no interstitial pneumonia at all) in situ hybridisation showed no positive signal, while immunohistochemical techniques showed only a few positive cells in lung tissue of one of nine patients. In addition to CMV-DNA analysis, formaldehyde-fixed, paraffin wax embedded tissue is amenable to immunohistochemical analysis with CMV monoclonal antibodies.     

Expression and regulation of CD97 in colorectal carcinoma cell lines and tumor tissues

The expression of CD97, a member of the EGF-TM7 family with adhesive properties, is proportional to the aggressiveness and lymph node involvement in thyroid tumors. CD97 has never been systematically investigated in other tumors. First, we examined colorectal carcinoma cell lines (n = 18) for CD97 expression and regulation. All cell lines were CD97-positive. The level of CD97 in each line correlated with migration and invasion in vitro. This result was confirmed in CD97-inducible Tet-off HT1080 cells. Transforming growth factor-beta, which inhibits proliferation in transforming growth factor-beta-sensitive LS513 and LS1034 cells, down-regulated CD97 in these cell lines. Examining CD97 during sodium butyrate-induced cell differentiation of Caco-2 cells, we could demonstrate a CD97-decreasing effect. Second, we screened 81 colorectal adenocarcinomas by immunohistology for expression of CD97. Normal colorectal epithelium is CD97-negative. Seventy-five of 81 of the carcinomas expressed CD97. The strongest staining for CD97 occurred in scattered tumor cells at the invasion front compared to cells located within solid tumor formations of the same tumor. Carcinomas with more strongly CD97-stained scattered tumor cells showed a poorer clinical stage as well as increased lymph vessel invasion compared to cases with uniform CD97 staining. In summary, CD97 expression correlates with dedifferentiation, migration, and invasion in colorectal tumor cell lines. Moreover, more strongly CD97-stained tumor cells at the invasion front of colorectal carcinomas indicate the involvement of the molecule in tumor migration and invasion.