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J S Coon

Publications and source records attributed to J S Coon.

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Blood group-related antigens as markers of malignant potential and heterogeneity in human carcinomas.

The expression of BGR-Ags is often aberrant in human carcinomas. The observation that BGR-Ag expression in human bladder carcinomas correlates with prognosis for patients with these tumors is especially interesting in light of the numerous reports of correlations between cell surface glycosylation and malignant phenotype in experimental animal tumors. Many observations suggest how this relation might be mediated. It seems reasonable to anticipate that the study of the BGR-Ags and their expression in carcinoma may emerge from its current predominantly descriptive phase and become an important part of the investigation of human tumor biology.

Antigens, Neoplasm↗

Significance of DNA abnormalities in primary malignant melanoma and nevi, a retrospective flow cytometric study.

DNA ploidy of melanocytic skin tumors from 87 patients (53 primary melanomas, 34 nevi) was determined by flow cytometry from routinely prepared paraffin blocks. Ploidy data correlated strongly with conventional morphological parameters. Only 1 of 34 nevi, but 13 of 53 melanomas were aneuploid. Among the melanomas, none of 21 levels I-III melanomas was aneuploid, but 13 of 32 levels IV and V melanomas were aneuploid. There was also a significant correlation between increasing Breslow thickness and the presence of DNA aneuploidy. For 33 melanoma patients with over 2 yr of follow-up (average, 7.1 yr), only 4 of 23 diploid tumors have recurred, but 9 of 10 aneuploid tumors have recurred. We conclude that the biological potential of melanocytic skin tumors is strongly linked to DNA aneuploidy. Since this parameter can be conveniently determined from paraffin blocks, determination of ploidy abnormalities in these tumors may be clinically useful.

Aneuploidy↗

Expression of blood-group-related antigens in carcinoma in situ of the urinary bladder.

Expression of epithelial ABH blood group antigens and the T (Thomsen-Friedenreich)-antigen was quantitatively studied by immunoperoxidase techniques in nine cystectomy specimens containing extensive carcinoma in situ (CIS), and also histologically benign epithelium. CIS areas typically showed abnormal expression of both ABH and T-antigens and a distinctive vascular architecture, revealed by endothelial ABH staining. Histologically normal epithelium generally was antigenically normal, but occasionally showed abnormalities of either ABH or T-antigens. Antigen expression was variable in histologically atypical epithelium, with significant segments showing abnormalities of either ABH or T-antigen, and sometimes of both antigenic markers. It is postulated that histologically benign, but antigenically abnormal, epithelium may represent low-grade CIS of the urinary bladder. Assessment of blood-group-related antigen expression in flat atypical epithelium of the urinary bladder may be useful for predicting the biologic potential of these lesions.

ABO Blood-Group System↗

Should flow cytometric DNA analysis precede definitive surgery for colon carcinoma?

Conventional prognostic parameters for colon carcinoma are predominantly determined after resection and have limited predictive value. For an evaluation of the significance of flow cytometric (FCM) DNA analysis in colon carcinoma, 56 invasive colon carcinomas were prospectively studied to compare DNA ploidy with established prognostic parameters obtained from pathologic examination of resected specimens. Objective parameters, i.e., depth of invasion and node status, were strongly linked to DNA ploidy; diploid tumors tended to be Astler-Coller stage A or B and nondiploid tumors stage C or D. Diploid and nondiploid tumors did not differ according to subjective criteria such as histologic grade and microscopic invasion of vessels and nerves. These results suggest that FCM DNA analysis may be a valuable tool in managing patients with colon carcinoma, since analysis of biopsies could indicate the likelihood of tumor spread before surgery.

Adult↗

H, peanut lectin receptor, and carcinoembryonic antigen distribution in keratoacanthomas, squamous dysplasias, and carcinomas of skin.

The distribution of blood group antigen H(O), peanut lectin receptor (PNL-R) (a precursor to the MN blood group antigens), and carcinoembryonic antigen (CEA) was examined in 15 squamous cell carcinomas, 10 keratoacanthomas, 17 squamous dysplasias, and 5 normal controls using immunoperoxidase techniques. All controls and 8 carcinomas, 10 keratoacanthomas, 14 dysplasias expressed H antigen. All controls and 9 carcinomas, 10 keratoacanthomas, 16 dysplasias expressed PNL-R antigen. CEA was present in 15 carcinomas, in trace amounts in 3 keratoacanthomas, in 6 dysplasias, and in 0 controls. The staining for H antigen and PNL-R in the carcinomas and dysplasias was disorganized, patchy, and less than that of normal epithelium, while staining in keratoacanthomas was uniform, with normal to increased intensity as compared to controls in 9 cases. CEA showed weak focal staining in 5 carcinomas, 8 dysplasias and 3 keratoacanthomas, and more intense and extensive cytoplasmic and membrane staining in 10 carcinomas and 5 dysplasias, and no cellular staining in 4 dysplasias and 7 keratoacanthomas. CEA was present in greatest amounts in the well-differentiated carcinomas and focal in the less-differentiated tumors. The well-differentiated carcinomas had a greater percentage of cells staining for H antigen and PNL-R. The pattern of staining for H, PNL-R, and CEA appears to distinguish keratoacanthomas from carcinomas and squamous dysplasias, and may be a useful adjunct to diagnosis.

ABO Blood-Group System↗

Surface charge distribution in normal and transformed rat bladder epithelial cells in vitro.

Cationized ferritin (CF) was used as an ultrastructural marker to study differences in the distribution and density of surface anionic charges between normal and neoplastic cells. In anchorage-independent cell systems, CF induces a redistribution of cell surface receptor-ligand complexes into clusters, patches, and caps on the surfaces of transformed cells, but not on the surfaces of normal cells. In the present report, the authors have, for the first time, extended the CF labeling studies to a system of anchorage-dependent, rat bladder epithelial cell lines: normal RBTC cells and RBTCC-8 carcinoma cells. Cells were grown to confluency and labeled with 500 micrograms/ml CF for 3 minutes. After completion of CF labeling, cells were incubated for 0, 15, 60, 120 minutes, or overnight and were fixed then with buffered glutaraldehyde for electron microscopy. The results show that (a) CF induces grouping of surface anionic charge sites into patches and clusters on RBTCC-8 carcinoma cells (CF covers 53.86 +/- 2.15% of the plasma membrane), but not on normal RBTC cells (CF covers the entire plasma membrane); (b) CF densities are well correlated to the cell surface sialic acid contents of RBTC (2.42 +/- 0.30 microM/10(9) cells) and RBTCC-8 cells (1.26 +/- 0.25 microM/10(9) cells); and (c) CF-labeled membrane is internalized at equal rates by RBTC and RBTCC-8 cells (30% in 15 minutes; 60% in 60 minutes; 70% in 120 minutes; 100% overnight). These data indicate that CF-induced patching of anionic sites is a surface characteristic that is common to anchorage-dependent and independent tumor cells. Mechanisms of CF patching in neoplastic cells are discussed.

Animals↗

Pathology of superficial bladder cancer with emphasis on carcinoma in situ.

The coexistence of carcinoma in situ in flat epithelium adjacent to tumors is prognostically significant and is associated with an increased incidence of tumor recurrence and invasion. Recent investigations have been aimed at finding markers that will help identify flat areas of dysplasia or low-grade papillary transitional cell carcinomas that have a high potential to evolve into invasive tumors. Both DNA and karyotype analyses, as well as cell surface markers, have been examined in some detail and could have clinical value in certain settings. The tumor DNA index as measured by flow cytometry of nuclei retrieved from deparaffined sections may be particularly useful as a predictor of tumor recurrences and, possibly, tumor invasion as well. The diagnosis of superficial disease rests on urine cytology and the histopathologic assessment of tissue biopsies; however, intra- and inter-observer reproducibility of tissue and cytologic diagnoses by pathologists is a significant problem. The application of new technologies, such as flow cytometric analysis of deparaffined nuclei, may reduce the subjectivity involved in the light microscopic assessment of pathology specimens.

Adenocarcinoma↗

Flow cytometric analysis of heterogeneity in blood group-related antigen expression in a human urinary bladder carcinoma cell line, 647V.

Previous immunohistological studies showed a relationship between expression of blood group-related antigens (BG-Ag) and invasive potential in human urinary bladder carcinoma, but the marked variability of antigen staining within many individual tumors has obscured the biological basis of this finding. We studied the expression of the A, H, and T (Thomsen-Friedenreich) BG-Ag by flow cytometry in a human bladder carcinoma cell line (647V) using fluoresceinated BG-Ag-specific lectins (Dolichos bifloris, Ulex europaeus, and Arachis hypogaea). Cell cycle compartments were quantitated by flow cytometry using propidium iodide staining. Expression of all three antigens was highly variable, but staining for each antigen produced a distinct profile. T antigen expression appeared independent of A or H antigen expression. Cell populations sorted by T antigen expression showed heritable antigenic differences persistent over many weeks in culture. However, much of the T antigen variability was nonheritable, since the stable staining profiles of the sorted cells were intermediate between the parental and the profiles obtained immediately after sorting. The nonheritable antigenic variation did not appear entirely explainable by cell size or cell cycle fluctuation. These results were confirmed by isolating 64 clones from the dim part of the T antigen staining profile, 19 of which had a persistently dim phenotype. The variability of BG-Ag expression by human bladder carcinoma cells in vitro may explain the staining patterns observed in the study of antigen expression in resected human bladder carcinomas.

ABO Blood-Group System↗

Prognosis in carcinoma of the urinary bladder based upon tissue blood group abh and Thomsen-Friedenreich antigen status and karyotype of the initial tumor.

Several markers of initial bladder carcinomas described recently may be clinically significant predictors of biological behavior of future recurrences. Comparison of the marker systems and assessment of the value of using multiple markers have been difficult, because the various markers have been studied in different patients. In this study, we compared four markers [chromosome mode, marker chromosomes, and expression of the ABH "blood group" antigens and the Thomsen-Friedenreich antigen (using immunoperoxidase or lectin immunoperoxidase methods)] in 39 patients presenting initially with low-stage bladder carcinoma and followed 3 to 11 years or until deep muscle invasion occurred. Each of the markers was significantly related to subsequent recurrences with deep muscle invasion, and each marker system was able to identify those patients with a very low risk of subsequent invasion. For detection of a subpopulation of patients with Grade II carcinomas who were at high risk for development of subsequent invasion, combinations of markers, especially hyperdiploidy and abnormal expression of the Thomsen-Friedenreich antigen, were significantly more effective than any single marker system.

ABO Blood-Group System↗

Blood group precursor T-antigen expression in human urinary bladder carcinoma.

Tumor deletion of the ABH blood group antigens (BGAg) heralds an unfavorable prognosis in human bladder cancer. The T antigen (Thomsen-Friedenreich antigen: TAg), a precursor of other BGAg, has previously been found in malignant but not most normal cells, in which the TAg is cryptic but can be unmasked with neuraminidase (NMD). We investigated the prognostic significance of TAg expression in bladder cancer by staining paraffin sections with a T-specific lectin (peanut agglutinin [PNA]) immunoperoxidase technic. Seventy-two cases of low grade, low stage bladder cancer, 21 cases of high grade bladder cancer, and 68 controls were studied. All normals expressed the TAg only after NMD treatment (Cryptic TAg+). The Grade III cancers, all invasive, either expressed the TAg (TAg+)(67%) or lacked T even after NMD (Cryptic TAg-) (29%), indicating that the T structure was lost rather than masked as in normal tissue. Thirty-nine per cent of 23 Grade I and II cancers which were TAg+ or Cryptic TAg- subsequently became invasive (Stage B), compared with 10% of 49 Cryptic TAg+ cancers. For 32 Grade I and II, ABH BGAg negative cancers, 64% of TAg+ or Cryptic TAg- cancers became invasive, compared with 17% of cancers which had Cryptic TAg+. Thus, the TAg may be a prognostically useful immunohistochemical tumor marker in bladder cancer, especially for tumors negative for ABH BGAg.

ABO Blood-Group System↗

Primary adenocarcinomas of the human urinary bladder: histochemical, immunological and ultrastructural studies.

Neoplastic and non-neoplastic tissue specimens from ten patients with primary adenocarcinoma of the urinary bladder were examined. Most of these tumors were associated with either foci of transitional cell carcinoma and/or with glandular metaplasia of the bladder epithelium. The mucin produced by the neoplastic cells was PAS, alcian blue, mucicarmine, PB/KOH/PAS, and RPB/KOH/PAS-positive. ABH isoantigens of these tumors were not always deleted. Ultrastructurally, the neoplastic cells resembled goblet cells. Their plasma membrane had numerous microvilli with prominent glycocalyx. Proliferation and attenuation of tight junctions were noted. The gap junctions were few and small. Two types of desmosomes were found. The ultrastructural features of the neoplastic cells were attributed in part to the malignant transformation and in part to the direction of their differentiation. We have not observed any distinctive morphologic, histochemical, immunologic or ultrastructural features that might be diagnostic for these adenocarcinomas.

Adenocarcinoma↗

Variability in the expression of the O(H) antigen in human transitional epithelium.

In many organs the so-called blood group antigens A, B and O(H) are constituents of the surface of normal epithelial cells. Deletion of these antigens in cases of carcinoma may serve as a clinically useful tumor marker, especially in cases of carcinoma of the bladder. Further progress is hampered by uncertainty concerning the detectability of A, B and H tissue isoantigens on normal urothelium in tissue sections. We examined th expression of these tissue isoantigens on normal ureteral urothelium obtained at autopsy from 68 adults using the specific red cell adherence test and found that they were not detectable in normal urothelium from a significant fraction of individuals in blood group O and that results in blood groups A, B and AB also were somewhat variable. The variability did not appear related to the secretor status or postmortem interval. Our results suggest that the current specific red cell adherence test may not be suitable for detecting deletion of tissue isoantigens in bladder tumor patients in blood group O.

ABO Blood-Group System↗

Detection of ABH tissue isoantigens by immunoperoxidase methods in normal and neoplastic urothelium. Comparison with the erythrocyte adherence method.

The expression of the ABH blood group antigens (BGAg) by carcinomas of the urinary bladder at the time of initial biopsy heralds a relatively benign clinical course, whereas antigen deletion in histologically similar tumors is often predictive of tumor recurrences and invasion. The use of BGAg as a tumor marker in the clinical setting has been limited by difficulties in demonstrating BGAg in tissue sections with the erythrocyte adherence test, especially for antigen H. In this study, immunoperoxidase methods were used to detect BGAg in deparaffinized tissue sections of normal and malignant human urothelium, and the results were compared with those of the erythrocyte adherence test performed on adjacent sections. Results with the two methods were similar for antigens A and B; however, a novel lectin-antilectin immunoperoxidase method was clearly superior for detecting antigen H. The immunoperoxidase method significantly reduced false-positive test results for antigen deletion in normal urothelium and more accurately predicted the subsequent clinical course in patients having urinary bladder cancer.

ABO Blood-Group System↗

Inverted papilloma of the urinary bladder: ultrastructural and immunologic studies.

The histologic, ultrastructural, and immunologic features of an inverted urinary bladder papilloma were studied with thin-section and freeze-fracture electron microscopy, a specific red blood cell adherence test, and through analysis of urine carcinoembryonic antigen (CEA). The increased number of gap junctions and desmosomes, the presence of thickened and reduplicated basal laminae, and the normal CEA levels found in association with this neoplasm, correlate well with its generally predictable benign behavior.

Aged↗

Proliferation of epithelia of noninvolved mucosa in patients with head and neck cancer.

BACKGROUND: Morphologically noninvolved mucosa in patients with head and neck cancer is altered by carcinogens. These alterations may include chromosome alterations, gene mutations, and other molecular abnormalities which may explain very high incidence of second tumors in this group of patients. The purpose of this study was to investigate the in vivo proliferative characteristics in epithelial tissues adjacent to the tumor in a series of patients with head and neck cancer. METHODS: Twenty-one patients with head and neck tumors received IV infusions of iododeoxyuridine (IdUrd) and/or bromodeoxyuridine (BrdUrd). Surgical specimens containing normal-appearing epithelium adjacent to the tumor were selected and stained with the respective monoclonal antibody. The percentage of S-phase cells (labeling index, LI) was counted in the basal and suprabasal layers of the epithelium. RESULTS: In 27 samples of oral epithelium obtained from 14 previously untreated patients, labeled (S-phase) cells were predominantly located in suprabasal layers with LI 31.6 +/- 3.1% (range 13.5-73.2%). In contrast, the LI of the basal layer was very low: 1.6 +/- 0.2% (range 0.5%-8.8%). There was no statistically significant difference between normal appearing and dysplastic samples (p > 0.05). In 10 samples obtained from 7 patients whose biopsies were studied 2 days to 2 month after concomitant radiation and chemotherapy, the LI of the oral mucosa basal layer was significantly higher (21.0 +/- 4.1%, range 6.3-39.2%). The LI of the suprabasal layer in treated patients was 14.3 +/- 2.4% (range 5.9-31.1%). The LI of nasal pseudostratified epithelium (4 samples) was 11.2%. The average LI of "basal" cells was 8.3% (range 5.9-11.9%) and that of "suprabasal" cells was 13.8% range (3.2-29.5%). The basal layer of the skin (5 samples) contained 9.3% labeled cells (range 3.3-16.3%); the LI of suprabasal layers of skin was 21.3% (range 7.8-33.2%). CONCLUSION: Both the frequency and the spatial distribution of S-phase cells are disordered in noninvolved epithelia in patients with head and neck tumors. These observations suggest that disordered proliferation may be an early consequence of field cancerization, a consequence that occurs prior to appearance of morphologically apparent hyperplasia or dysplasia.

Carcinoma, Squamous Cell↗