Expression Of Blood Group-related Antigens Research Articles

Expression of blood group-related antigens in neoplastic uterine cervix

Expression of blood group antigens in normal, displastic and tumoral uterine cervix from 35 hysterectomised women with carcinoma of the cervix was investigated; the results were correlated with patients' ABH phenotype and secretor status. We used an indirect immunoperoxidase technique and a panel of monoclonal antibodies and lectins directed against different antigenic specificities. Anomalous expression of blood group antigens in premalignant lesions from cervix was found. Partial loos of expression of blood group antigens and some lectins in different grades of cervical intraepithelial neoplasia, and a total loss of expression in CIN III and in infiltrating carcinoma of the cervix from secretor patients was revealed. The findings herein described confirm the importance of these antigens as tumour markers and they might be useful for the study of cervical carcinogenesis.

Aberrant glycosylation based on the neo-expression of poly-N-acetyllactosamine structures in squamous cell carcinomas of the head and neck.

An immuno- and lectin-histochemical study was performed to investigate the aberrant expression of blood group-related antigens and poly-N-acetyllactosamine structures in squamous cell carcinomas of the maxillary sinus, the larynx, the apipharynx, the hypopharynx, the oral cavity, the parotid gland and the tonsil from 52 patients using monoclonal antibodies against A, B and H antigens, and six lectins, UEA-I, PNA, VVA-B4, PWM, LEA and DSA. In addition, GSA-II staining following endo-beta-galactosidase digestion procedure was also applied. A, B and H antigens were expressed in most normal epithelial cells of head and neck organs, and depended on the patient blood type. However, in squamous cell carcinoma, A antigen was not detected in eight out of 25 individuals of blood groups A and AB, although B antigen was consistently expressed in carcinoma cells from all the B and AB individuals. On the other hand, H antigen was expressed in carcinoma cells not only from all blood group O individuals, but from 32 out of 35 individuals of blood groups A, B and AB. T and Tn antigens, which are recognized by PNA and VVA-B4, were strongly expressed in carcinoma cells from 40 and 42 out of 52 individuals respectively. Reactivity with GSA-II staining following endo-beta-galactosidase digestion, which recognizes linear poly-N-acetyllactosamine structures, was found in a few malignant cells from 21 individuals. Staining with anti-A, -B and -H monoclonal antibodies and UEA-I lectin was diminished after endo-beta-galactosidase digestion in some cases. Lectins specific for poly-N-acetyllactosamine, such as PWM, LEA and DSA, exhibited reactivity in some malignant cells from 30, 22 and 32 out of 52 individuals respectively. These results suggested that the expression of the blood group-related antigens is suppressed and immature carbohydrate chains, that is H, T and Tn antigens, are accumulated in squamous cell carcinomas of the head and neck. The results further suggested that poly-N-acetyllactosamine structures are simultaneously synthesized along with the deletion of A antigen and the accumulation of precursors.

Expression of blood group-related antigens in cholangiocarcinoma in relation to non-neoplastic bile ducts.

The abnormal expression of blood group related antigens has been reported in many malignant tumours; however, such expression in cholangiocarcinoma has not been examined systematically. The expression of blood group-related antigens (A, B, H, Lewis(a), Lewis(b), Lewis(x), Lewis(y), carbohydrate antigen 19-9 and carcinoembryonic antigen) was investigated immunohistochemically in 75 cases of cholangiocarcinoma (31 peripheral type and 44 hilar type). In non-neoplastic bile ducts, A, B, and H antigens were expressed in large bile ducts, while Lewis(a,b,y) and carbohydrate antigen 19-9 were variably expressed in both large and small bile ducts. Lewis(x) and carcinoembryonic antigen was not found in non-neoplastic bile ducts. In cholangiocarcinomas, A, B, and H, antigens were more frequent in the hilar type than in the peripheral type, although the difference was not significant. The expression of the blood-group related antigens, particularly A, Lewis(a,b,y), carcinoembryonic antigen, and carbohydrate antigen 19-9, was frequent in the tumour cells in well differentiated adenocarcinomas, while their immunoreactivity was less frequent in poorly differentiated adenocarcinomas. The superanuclear and luminal expression of these antigens in carcinoma cells was frequent in well differentiated adenocarcinomas, and the diffuse, cell membranous and stromal expression of these antigens was relatively frequent in poorly differentiated adenocarcinomas and adenosquamous carcinoma. The A, B, and H immunoreactivity of both non-neoplastic bile ducts and cholangiocarcinomas was consistent with the host blood group type. These findings suggest that both the expression and intracellular distribution of blood group-related antigens in cholangiocarcinoma are related to the differentiation of cholangiocarcinoma and, possibly, to the parent structure.

Aberrant expression of carbohydrate antigens in squamous cell carcinoma of the tongue

An immunohistochemical study was performed to observe the aberrant expression of blood-related group antigens in squamous cell carcinomas of the tongue from 10 patients and 13 normal tongue tissues using seven monoclonal antibodies, A, B, H, X001, H001, Lea and Leb, and four lectins, PNA, VVA-B4, UEA-1 and LTA. In SCC, Leb antigens were expressed in all cases examined (10 cases). T and Tn antigens which were examined with PNA and VVA-B4 stains, were expressed in seven out of 10 and six out of 10 cases, respectively, while these two antigens were not found in normal tissues. A, B and H antigens were expressed in most normal tongue epithelial cells, strictly dependent on the patient blood type. But in SCC, A and B antigens were not detected in five out of seven cancer cells from blood group A, B and AB individuals, whereas H antigen was expressed in 5 out of 7 cancer cells from blood group A, B and AB individuals. These results suggest that the expression of blood group-related antigens in suppressed to that of more immature carbohydrate chains in the setting of tongue cancer.

The relationship between the expression of blood group-related antigens and the cell proliferation of pancreatic carcinomas induced by N-nitrosobis(2-oxopropyl)amine in hamsters.

The relationship between expression of blood group-related antigens (BGRAs) A, B, H, and cell proliferation was investigated during pancreatic carcinogenesis and in transplanted pancreatic carcinomas induced by N-nitrosobis(2-oxopropyl)amine in hamsters. Immunohistochemical staining was performed using monoclonal antibodies (MoAbs) against BGRAs A, B, H, and bromodeoxyuridine (BrdU). The labeling index (LI) was determined as the ratio of the number of BrdU-labeled cells to the total number of cells counted in each lesion. During carcinogenesis, the LI was observed to increase in line with the increase in the extent of atypism (P < 0.01). The mean LIs of the hyperplasia, atypical hyperplasia, and carcinoma were 0.32, 3.21, and 10.2, respectively. The mean LIs of transplanted carcinomas were higher than those of the original carcinomas (P < 0.01). The reactivity with each of the antibodies was determined using an arbitrary scoring system. Staining with MoAbs A and B (staining intensity; 1+ to 3+) appeared to be more intense than that with MoAb H (1+ to 2+) during carcinogenesis. Regarding the growth rate, which was very high, in the transplanted carcinomas, MoAb A reacted with all the cancer cells (4+), whereas, MoAbs B and H reacted with fewer cells (1+ to 3+). These results indicate that the A antigen in particular is associated with the cell proliferation of pancreas, especially with carcinoma induced in hamsters.

Expression of blood group-related antigens in normal and malignant pancreatic tissue correlated with genotype of the patient defined by saliva glycoprotein.

Seven murine monoclonal antibodies (MoAb) detecting blood group antigens of the Lewis system and their sialylated derivatives were used to define their immunohistochemical distribution in normal and malignant pancreatic tissues. The specific blood group antigens studied included Lewis(a) (Le(a)), Lewisb (Leb), Lewisx (Le(x)), Lewis(y) (Le(y)), sialyl-Lewis(a) (s-Le(a)), sialyl-lacto-N-tetraose (s-LNT), and sialyl-Lewisx (s-Le(x)). The expression of these antigens was analyzed by immunoperoxidase technique in pancreatic tissue of patients with (n = 27) and without (n = 19) pancreatic cancer. The genetic background of their secretor status and their Lewis phenotypes were determined by the enzyme-linked immunosorbent assay using purified salivary glycoprotein and MoAb against eight different blood group-related antigens (Le(a), Leb, Le(x), Le(y), H1, H2, A, B2), and the putative genotypes of the patients were classified as follows: SeLe, Sele, seLe, and sele. The following results were obtained: (1) In normal pancreas, Le(a), s-Le(a), s-LNT, and s-Le(x) were expressed in ducts, but their expression was restricted to the luminal side of the cytoplasm (cytoplasmic type with positive polarity). Leb and Le(y) showed similar patterns of expression in ducts and some parts of the acinus. In contrast, Le(x) was absent in most cases. (2) Expression of Leb was observed in normal pancreatic ducts in all 46 patients, regardless of their genotypes. Le(a) and s-Le(a) were not expressed in specimens from patients with the seLe and sele saliva phenotypes. (3) In pancreatic cancer, the following antigens were expressed cytoplasmically in the proportion of cases indicated: Le(a) (78%), Leb (85%), Le(x) (33%), Le(y) (44%), s-Le(a) (78%), s-LNT (89%), and s-Le(x) (85%). They also were detected in the surrounding stroma. This pattern of expression is distinct from that found in normal pancreatic tissue. Patients with Sele and sele genotypes did not express Le(a) or s-Le(a), except in one case. (4) Serum levels of carbohydrate antigen 19-9 (CA 19-9) were not elevated in patients with pancreatic cancer with the Sele and sele genotypes but were elevated in most patients with SeLe and seLe genotypes. The overall findings indicate that Lewis-related antigens act as pancreatic tissue-related antigens, depending in part on salivary phenotypes of the patient. With proper antigen selection and the determination of secretor status, these anti-blood group MoAb may be of clinical utility in the diagnosis of pancreatic cancer.

Expression of blood group-related antigens, ABH, Lewis(a), Lewis(b), Lewis(x), Lewis(y), CA19-9, and CSLEX1 in early cancer, intestinal metaplasia, and uninvolved mucosa of the stomach.

The expression of blood group-related antigens, A, B, H type 2, Lewis type 1 (Lewis(a) [Le(a)] and Lewis(b) [Le(b)]), Lewis type 2 (Lewis(x) [Le(x)] and Lewis(y) [Le(y)]), sialylated Le(a) (CA19-9), and sialylated Le(x) (CSLEX1), was analyzed sequentially with immunohistochemical methods in early gastric cancer, intestinal metaplasia, and uninvolved gastric mucosa obtained from 35 surgical specimens of patients who underwent gastrectomy. The high incidence of the inappropriate expression of Lewis type 1 antigens and the deletion of H and Lewis type 2 antigens was observed similarly in patients with cancer and intestinal metaplasia. The acquisition of CA19-9 and CSLEX1 and the deletion of B antigen frequently were found in intestinal-type cancer and all types of intestinal metaplasia. The simultaneous deletion of A antigen was detected only in the combination of intestinal-type cancer and incomplete-type intestinal metaplasia. Thus the present study shows that similar changes of tissue antigenicities exist in early gastric cancer and intestinal metaplasia.

Correlation between morphology and blood groop-related antigen expression in pancreatic tumors induced in Syrian hamsters

Expression of blood group-related antigens (BGRAs) A, B, H, Le(b), Le(x) and Le(y) was examined immunohistochemically in neoplastic and hyperplastic lesions induced by N-nitrosobis(2-oxopropyl)amine in Syrian hamsters to determine a relationship between histological and biological patterns of the lesion and expression of BGRAs. With the exception of papillary ductal cell hyperplasia, A-antigen discriminated between the benign and malignant lesions far better than the other antigens, which showed heterogeneity in the expression of benign and malignant tumors. However, production of A-antigen decreased with the degree of tumor dedifferentiation and was absent in anaplastic regions of tumors. Marked differences were found in the expression of A- and B-antigen in tubular complexes, one of the earliest induced changes, in relation to the type of cells populating these lesions. Overall, B-antigen seemed to be associated more with benign cells than malignant cells. On the other hand, Le(x)-antigen was expressed primarily in the invasive portion of some cancers and seemed to reflect active proliferative processes.

Blood group antigen expression in developing pancreas and in induced pancreatic cancer cells in Syrian hamsters

Expression of blood group-related antigens and the binding pattern of Ulex europaeus-I (UEA-I) in fetal and newborn hamster pancreases was examined immunohistochemically by monoclonal antibodies (MoAbs) against blood group antigens and by peroxidase-conjugated UEA-I. The fetal hamster pancreas was detected histologically at the 12th day of gestation. MoAbs A, B and Le(a) were not immunoreactive with pancreatic cells in any stage of development nor were they after birth. Le(x) was first expressed in the luminal surface of duct cells at the 13th day of gestation, disappeared at the 15th day of gestation, was re-expressed after birth in acinar cells and was absent in the adult pancreas. Le(b) and Le(y) were expressed in acinar cells in late fetal and early newborn stages, but disappeared with maturation and were absent in the adult pancreas. UEA-I binding, however, was demonstrated in both fetal and adult pancreatic tissue. In cancer cells induced by BOP, blood group antigens except for Le(a) and UEA-I binding were found in various reactivity. These findings suggest that in hamsters (i) A and B antigens are tumor-related antigens; (ii) H, Le(b), Le(x) and Le(y) are oncofetal antigens; and (iii) fucosylation is an important event in cell differentiation.

Expression of blood group-related antigens in the intrahepatic biliary tree and hepatocytes in normal livers and various hepatobiliary diseases.

The distribution of blood group-related antigens (A, B, H, Lea and Leb) in the intrahepatic biliary tree and hepatocytes was studied by immunoperoxidase techniques. In normal livers, large and septal bile ducts expressed A and B antigens in the cases with comparable blood groups and also expressed H antigen frequently in the cases with blood group O, A or B, and infrequently in the cases with AB. Lea and Leb were found in biliary cells at any level in secretors. In hepatobiliary diseases, A, B and H were neoexpressed in the interlobular bile ducts in addition to their expression in the large and septal bile ducts. Lea and Leb were found in almost all proliferated bile ductules and in some hepatocytes, especially those adjacent to ductules, in any of the hepatobiliary diseases, and their expression seemed parallel to the disease activity. H antigen was also neoexpressed in some hepatocytes and proliferated bile ductules. Extramural peribiliary glands expressed H, Lea, Leb and, to a lesser degree, A and B antigens in normal and pathologic conditions. This study disclosed that the normal biliary tree has a specific expression of blood group antigens at different levels and that this expression is altered in pathologic conditions. Periportal hepatocytes showed neoexpression of blood group antigens in pathologic conditions, and some of these hepatocytes may undergo ductular metaplasia.

Establishment of hamster pancreatic ductal carcinoma cell line (PC-1) producing blood group-related antigens

A pancreatic cancer cell line, PC-1, was established from a pancreatic ductal carcinoma induced in a hamster by N-nitrosobis(2-oxopropyl)amine (BOP). The cells grew in a monolayer with a doubling time of 38 h, and floated or piled up to form a duct-like structure. Chromosome counts ranged from 42 to 89. Light and electron microscopic studies of PC-1 cells revealed production of conspicuous amounts of amorphous substance. Injection of PC-1 cells into the homologous hamster pancreas resulted in tumor formation, histopathologically indistinguishable from the original primary pancreatic ductal carcinoma. Immunohistochemical expression of blood group-related antigens (BGRAs), A, B, H, Leb, Lex and Ley was observed both in the cells in the culture, and in tumor transplanted into the pancreas. In the culture supernatant, a high titer of blood group A antigen was detected. This cell line may provide a unique tool for studying the mechanism of BGRA synthesis and release in malignant cells.