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PubMed1979

Blood group isoantigen deletion in carcinoma in situ of the urinary bladder.

Blood group isoantigens A and H (O) were measured by the Secific Red Cell Adherence (SRCA) Test in nine radical cystectomy specimens removed from patients with extensive carcinoma in situ of the urinary bladder. All bladders had areas of histologically normal epithelium and areas of epithelial atypia in addition to the carcinoma in situ. In eight cases, tissue-associated blood group isoantigens were deleted in areas showing either atypia or carcinoma in situ. Isoantigens were present in these areas in the ninth case. Blood group isoantigens were absent in approximately half of the sections of histologically normal epithelium. We propose that areas of epithelium which appear benign according to conventional histological criteria but in which the blood group isoantigens are absent may represent areas of low grade carcinoma in situ.

ABO Blood-Group System↗
PubMed1985

ABH blood group isoantigen expression in breast carcinomas--an immunohistochemical evaluation using monoclonal antibodies.

The ABH blood group isoantigen status of a retrospective series of 233 invasive breast carcinomas was examined, employing monoclonal antibodies (MCAB) against A, B, and H antigens with the avidin-biotin-peroxidase complex method. In addition, the H antigen was localized with Ulex Europeus Agglutinin I (UEAI) binding. The MCABs provided consistent and specific staining of erythrocytes and endothelium, as well as normal and neoplastic breast epithelium. The anti-H MCAB yielded cleaner background and less intense staining, but otherwise the staining distribution was comparable to the UEA I technique. Contrary to previous reports, deletion of isoantigen expression was not universal in all invasive carcinomas. Whereas 64%, 77%, and 73% of carcinomas from groups A, B, and AB patients, respectively, demonstrated total isoantigen loss, the remaining tumors exhibited variable degrees of isoantigen expression. Moreover, those carcinomas with complete loss of A and B determinants still displayed variable degrees of H immunoreactivity. Carcinomas from group O patients had different degrees of H antigen deletion, with only 12% showing total loss. Statistical analysis revealed that the isoantigen status bore no significant relationship to various epidemiologic, clinical, and pathologic parameters and did not serve as a useful prognostic determinant.

ABO Blood-Group System↗
PubMed1987

ABH isoantigens in bladder carcinoma patients grouped according to DNA changes over time.

Eighteen patients with transitional cell bladder carcinoma and increasingly abnormal ploidy were assembled to evaluate the relation over time between ploidy and ABH isoantigen deletion. Fifteen patients with diploid recurrent tumors and 16 with aneuploid tumors over time were used as controls. ABH isoantigen deletion at diagnosis was closely related to cancer death, while isoantigen assessments on recurrences gave less prognostic information. Aneuploidy at diagnosis also indicated an adverse prognosis, as did recurrent bladder carcinoma with deteriorating ploidy. Patients with tumors deleted of isoantigen expression at diagnosis but with normal ploidy had as bad a prognosis as patients with deleted tumors and aneuploidy, indicating that isoantigen deletion may occur earlier than ploidy changes.

Adult↗
PubMed1975

Antibody-induced redistribution of CEA on the cell surface: utilization in separation of CEA and isoantigen A.

Antibodies specific for carcinoembryonic antigen (CEA) induced polar redistribution of CEA which was expressed on the surface of human intestinal carcinoma cells grown in tissue culture. Polar redistribution occurred at 23 degrees C and 37 degrees C but not at 4 degrees C and was inhibited by sodium azide and cytochalasin B. Antibodies to isoantigen A did not react with CEA at the cell surface but did react with isoantigen A which was not redistributed by the antibody. Cells which expressed both CEA and isoantigen A were used to demonstrate that polar redistribution of CEA could be induced without altering the distribution of isoantigen A. The data indicate that CEA and isoantigen A can be expressed on the same cell as separate molecules.

ABO Blood-Group System↗
PubMed1979

Isoantigens A, B, H in normal skin and tumors of the epidermal appendages.

Isoantigens A, B, H(O) in biopsy specimens of 26 normal skin and in 35 adnexal tumors were studied by the red cell adherence (RCA) test of Davidsohn. Isoantigens were detected in the stratum corneum, stratum granulosum, stratum spinosum, acrosyringium, keratogenous zone of hair follicle, eccrine duct, and eccrine gland. The apocrine gland and duct consistently had negative test results for isoantigens. Seventy percent of all tumors tested contained isoantigens and included syringoma, hidrocystoma, syringocystadenoma papilliferum, spiradenoma, eccrine poroma, dermal duct tumor, clear cell hidradenoma, and cylindroma. We interpreted the presence of isoantigens in adnexal tumors as being evidence of immunologic maturity with differentiation toward eccrine structures. The RCA test is a new, sensitive, immunologic technique that can complement enzyme histochemical stains and electron microscopy in the study of the histogenesis of adnexal skin tumors.

ABO Blood-Group System↗
PubMed1988

Blood group isoantigen deletion and chromosomal abnormalities in bladder cancer.

The presence or absence of blood group isoantigens in 78 patients with transitional cell carcinoma of the bladder was correlated with tumor stage and grade, and results of chromosomal analysis. For blood group isoantigen detection the indirect immunoperoxidase method with monoclonal antibodies to A, B and H antigen was used. In 51 per cent of the 59 superficial tumors blood group isoantigens were demonstrable, whereas all deeper infiltrating and higher grade tumors were negative. However in superficial tumors the mode of blood group isoantigen expression did not correlate significantly with tumor recurrence and progression. A consistent correlation was demonstrated among chromosomal numbers, tumor grade and clinical course. The chromosomal abnormalities found and mode of blood group isoantigen expression, even in combination, had no prognostic value additional to the grading criteria used.

ABO Blood-Group System↗
PubMed1986

Intramammary lymphatic invasion in breast carcinomas. Evaluation using ABH isoantigens as endothelial markers.

Recent studies indicate that intramammary lymphatic invasion represents an important prognostic parameter in breast carcinomas. However, the identification of intramammary lymphatic invasion in tissue sections is a subjective procedure, frequently hampered by factors such as fixation artefacts and interobserver variations. In this study, monoclonal antibodies to ABH isoantigens were applied on formalin-fixed, paraffin-embedded breast carcinoma tissue by using the avidin-biotin-peroxidase complex technique. In addition, the H antigen was localized using the Ulex europeus agglutinin I lectin binding technique. Isoantigen localization provided excellent delineation of lymphatics and blood vessels, in general unhampered by the retention of isoantigen expression in some breast carcinomas. In comparison, Factor VIII-related antigen localization required prior trypsin enhancement and was less sensitive and less consistent. The staining for isoantigens was more intense in vascular than in lymphatic endothelium. ABH isoantigen localization of lymphatic channels identified lymphatic tumor emboli peripheral to and within the carcinomas, and distinguished bona fide intramammary lymphatic invasion from tissue shrinkage artefacts. The applicability to routinely processed tissue permits retrospective studies and renders the identification of intramammary lymphatic invasion a more objective procedure. Further studies are needed to assess the role of this technique in evaluating the prognostic value of intramammary lymphatic invasion; the technique may be extended also to the study of other neoplasms.

ABO Blood-Group System↗
PubMed1985

Fluorescence methods for measuring the A, B, and H isoantigens on cytological material from bladder carcinoma.

Fluorescence methods for determining ABH isoantigens on transitional cells were developed for the study of cytologic material. Indirect immunofluorescence was used for A- and B-antigens, fluorescein-labeled Ulex Europaeus lectin for the H-antigen. Isoantigens of 151 patients with bladder carcinoma were studied. Patients with a malignant cytology showed deletion in 31/65 cases compared to 12/62 cases when the cytology was benign. Cyto-flow ploidy determinations were abnormal in 41/120 cases measured; cells from 21 of these 41 had isoantigen deletion compared to 25/79 cases with a diploid pattern. The ABH isoantigen deletion shows some relation to malignant cytology, abnormal ploidy and a visible tumor, but is probably an independent parameter.

ABO Blood-Group System↗
PubMed1966

Immunoglobulin isoantigens (allotypes) in the mouse. II. Allotypic analysis of three gammaG2-myeloma proteins from (NZB x BALB/c)F1 hybrids and of normal gammaG2-globulins.

Further analysis of the isoantigens (allotypes) of 2 classes of normal mouse immunoglobulins, gammaG(2a) and gammaG(2b), has shown a minimum of 10 specificities for the Ig-1 locus (controlling gammaG(2a)-antigens) and 3 specificities for the Ig-3 locus (controlling gammaG(2b)-antigens). Three gammaG(2)-myeloma proteins of plasma cell tumors induced in (NZB x BALB/c)F(1) mice have been analyzed for the isoantigens they carry. NZB mice are genotypically Ig-1(e) Ig-3(e), while BALB/c are Ig-1(a) Ig-3(a). Two of the myeloma proteins are gammaG(2a)-globulins. One of these, GPC-7, carries all the isoantigenic specificities of the Ig-1(e) allele while the other, GPC-8, carries all the isoantigenic specificities of the Ig-1(a) allele. Thus only one of the parental alleles of the mouse in which the tumor arose is expressed in each of these myeloma proteins. The third myeloma protein GPC-5, also carries the antigens of only one parental strain (NZB). However GPC-5, a gammaG(2b)-globulin, carries only one of the Ig-3 specificities normally associated with gammaG(2b)-globulins of NZB. Most remarkably it also carries one Ig-1 specificity normally associated with gammaG(2a)-globulins of NZB. This is the first analyzed mouse myeloma shown (a) to express some but not all the antigenic specificities normally associated with an allele and (b) to carry antigenic specificities controlled by two distinct immunoglobulin loci. The implications of these findings are discussed in relation to the genetic control of immunoglobulins.

Animals↗
PubMed1977

Isoantigens A, B, and H in morphologically normal mucosa and in carcinoma of the larynx.

A modified Coombs' mixed cell agglutination reaction was performed on biopsy specimens of 24 patients with squamous cell carcinoma of the larynx. Isoantigens A, B, and H(O) were absent in 15 cases, partially lost in eight, and completely retained in one case. In four cases the initial biopsy specimens were histologically benign yet negative for isoantigens. In subsequent biopsies these showed the presence of carcinoma. The morphologically normal-appearing squamous mucosa adjacent to a carcinoma was found to be devoid of isoantigens in ten cases. The investigation suggested that isoantigenic alteration as detected by mixed cell agglutination reaction was a sensitive sign, since it occurred in squamous mucosa prior to recognizable morphologic change for malignancy. The reaction may represent a functional dedifferentiation in cancerous tissue, analogous to but sometimes preceding morphologic dedifferentiation. The results were comparable to those in previous studies of neoplasms of various other anatomic sites.

ABO Blood-Group System↗
PubMed1983

Isoantigens A, B, H(O) in nasopharyngeal carcinoma.

Fifty cases of nasopharyngeal carcinoma (NPC) and its metastasis in ten lymph nodes were studied for specific red cell adherence (SRCA) to determine if any loss of blood group isoantigens was present to explain some of the differences such as their preponderance in local Chinese population and variable clinicopathologic behavior. While a patchy positive SRCA was noted on the surface of tumor cells in all cases of NPCs, it was not so in any of their metastasis. The findings suggest that in NPCs a few tumor cells may be capable of partially retaining isoantigens, and that this is neither influenced by their histologic type nor in any way seems to account for the variable prognosis. While the exact mechanism for negative SRCA in metastatic deposits in lymph nodes is unknown, it is possible that metastatic tumor cells may have lost isoantigens on reaching lymph nodes. The remote possibility of a 'preferential discharge' of isoantigen-free tumor cells from the primary tumor seemed unlikely in view of a mildly positive SRCA in all the NPCs.

ABO Blood-Group System↗
PubMed2002

Effect of tissue fixatives on the immunohistochemical expression of ABH blood group isoantigens.

Immunohistochemical analysis of ABH blood group isoantigens has been shown to be a useful ancillary technique for resolving problems associated with specimen mix-ups in the daily practice of surgical pathology. However, the effects of different fixatives on the expression of these antigens in paraffin-embedded tissues are not known. Therefore, the effects of seven different fixatives on the immunohistochemical expression of ABH blood group isoantigens were studied in tissues from several organs. The following fixatives were used: acetone, 70% ethanol, B5, Bouin, Carnoy, methanol, and 10% formalin. After fixation for 6, 12, and 72 hours, the tissue blocks were embedded in paraffin, and immunohistochemistry was performed on 4 microm-thick tissue sections using monoclonal antibodies to blood group isoantigens (A, B, and H) and the avidin-biotin detection method. Also, immunostaining was performed on step tissue sections with and without antigen retrieval using citrate buffer at pH 6.0. The expression of the blood group isoantigens was concordant with the blood group of the patient in all the cases studied, irrespective of the fixative and time of fixation. However, in the absence of antigen retrieval, the intensity of the staining reaction was diminished. These results showed that irrespective of the fixative used, immunohistochemical staining of paraffin-embedded tissue sections with ABH blood group antibodies is a rapid, reliable, and cost-effective method for sorting out interpretative problems of tissue contaminants (floaters) and specimen mix-ups in surgical pathology.

ABO Blood-Group System↗
PubMed1975

Carcinoembryonic antigen: evidence for multiple antigenic determinants and isoantigens.

Carcinoembryonic antigen (CEA) preparations, from various sources were compared by radioimmunoassay. The preparations studied included four CEA standards (CEA-Roch, CEA-Montreal, CEA-City of Hope, and CEA-British) and CEA from serum and liver metastases of a patient with cancer of the colon who had an extremely high concentration of serum CEA (more than 26,000 ng/ml). The data indicate that the CEA-Roche standard differs significantly from the other three CEA standards tested, and that the serum CEA from the patient was antigenically different from currently available CEA standards as well as from the CEA obtained from the patient's own liver metastases. These antigenic differences were reflected in radioimmunoassay inhibition curves that were different and that were not affected by perchloric acid extraction of CEA. Because of the antigenic variation in the serum CEA, markedly different CEA concentrations (varying by three orders of magnitude) were measurable by two different antisera (Roche and Montreal). All the various CEA standards and samples cochromatographed on columns of Sepharose-6B, despite the large antigenic variation. We postulate that CEA consists of a family of "isoantigens" with multiple antigenic determinants. We identified a serum CEA isoantigen that was different from the currently available standards. Consequently, we believe that results of radioimmunoassays currently used for CEA measurement may not represent absolute concentrations of serum "CEA", but may reflect the binding affinity of different isoantigens to a particular polyvalent CEA antiserum.

Carcinoembryonic Antigen↗
PubMedDate not supplied

The distribution of ABO(H) isoantigens in urinary bladder tumours.

The distribution of blood group isoantigens (ABH) was studied with the specific red cell adherence test (SRCA); the red blood cells were visualized by the benzidine-peroxidase reaction. The H antigen was detected with Ulex europaeus agglutinin I lectin by direct immunoperoxidase technique. One hundred and seven bladder tumours were tested. It was found that blood group isoantigens diminished with immaturity (grade) and tumour invasiveness (T stadium). Patients with ABH blood group isoantigen deletion should be considered to be belong to a particularly high-risk group. The preservation of blood group antigens in grade II-III carcinomas may be useful in the choice of treatment (conservative or radical). In six cases in the area of squamous metaplasia of invasive carcinomas a strong false SRCA reaction was noticed detecting presumably the blood group determinants of the epidermal growth factor receptors.

ABO Blood-Group System↗
PubMedDate not supplied

Loss of blood isoantigens in exfoliated cells during the progression of CIN demonstrated by monoclonal antibody staining.

The presence of isoantigens A, B and H in exfoliated cervical epithelial cells was readily demonstrable in cervical smears using monoclonal antibodies and an immunoperoxidase staining technique. The progressive decrease in the percentage of immunoperoxidase-positive dysplastic cells and in the proportion of cytologically normal squamous cells associated with these dysplastic cells reflected the loss of isoantigen expression that paralleled increasingly severe stages of cervical intraepithelial neoplasia. The loss of isoantigen expression in morphologically normal epithelial cells and in dysplastic cells may indicate that a particular patient is at greater risk of disease progression and that close follow-up is warranted.

Antibodies, Monoclonal↗
PubMed1987

[The study of the ABH isoantigen of bladder tumors].

ABH isoantigens in 82 cases with bladder tumor of various grades and stages were investigated by the avidin-biotin-peroxidase complex (ABC) method. Correlation of ABC expression for isoantigens with pathological findings on the grading and staging system of the bladder tumors were as follow: Of 60 cases of low grade tumors, 34 (56.7%) were positive and of 22 cases of high grade tumors, 21 (95.5%) were negative. Of 63 cases of low stage tumors, 35 (55.6%) were positive and all 19 cases of high stage tumors, (100%) were negative. The isoantigens in the tissue of the bladder tumors tended to disappear as the histologic anaplasia of the tumor progressed. There was a high correlation between the histological grade, stage and ABC expression (p less than 0.01). In a follow-up study of 38 patients with low grade, low stage, initial transitional cell carcinoma, 9 of the 24 patients positive for ABC expression (37.5%) showed recurrence during the 1 to 6 year follow-up period, whereas 10 of the 14 patients negative for ABC expression 10 (71.4%) did. There was a high correlation between the recurrence rate and ABC expression (p less than 0.05). Therefore, the analysis in the bladder tumors may be valuable for prediction of malignant potential, especially for the low grade, low stage tumors.

ABO Blood-Group System↗
PubMed1973

Loss of isoantigens A, B and H in prostate.

Formalin-fixed tissues from 65 prostates were grouped and investigated by the technic of mixed cell agglutination reaction (MCAR) for studying isoantigens A, B and H. The results of this study indicated that the MCAR was strongly positive at the epithelium of the acini in the majority of patients with benign prostatic hyperplasia. On the other hand, patients with primary carcinomas and metastatic carcinomas of prostates were found to be uniformly negative for any agglutination reaction. Prostates from a group of younger individuals only showed a patchy distribution of the MCAR at the epithelium of the acini. In view of these findings, it seemed that the traces of isoantigens in normal prostates show a considerable increase when the disease process of BPH becomes manifest in this organ, while in cases of primary and metastatic carcinomas the isoantigens are totally lost. In the light of previous studies on similar lines, the various possible mechanisms for this sudden transition are discussed.

Adenocarcinoma↗
PubMed1976

Isoantigen loss in cervical neoplasia. Demonstration by immunofluorescence and immunoperoxidase techniques.

Tissue sections from normal uterine cervix and from uterine cervices with dysplasia, carcinoma in situ, and invasive cancer were studied in 70 instances using immunofluorescence and immunoperoxidase techniques for demonstrating the presence of isoantigens A and B. Isoantigens were demonstrated in normal squamous epithelium. Antigens were lost in foci of invasive cancer, were considerably reduced or lost in areas of classic carcinoma in situ in all cases, and were reduced in most cases of dysplasia. These observations confirm those obtained with the specific red cell adherence test. The results suggest that immunofluorescence and immunoperoxidase techniques are sensitive, reproducible, easily performed methods for demonstrating the loss of isoantigens in cervical neoplasia.

Carcinoma in Situ↗