bromochloroacetic-acid and Schistosomiasis-haematobia

The main distinctive feature of carcinoma in schistosomal bladder is keratinized squamous cell carcinoma. Keratins/cytokeratins constitute a multigeneic family of structurally related polypeptide markers for the malignant state of epithelial cells. A monoclonal antibody (UNME/K1) regognizing keratins associated with squamous cell carcinoma of the human urinary bladder was generated at the Urology and Nephrology Center, Mansoura, Egypt (UNME), by fusion of spleenocytes from a BALB/c mouse immunized with a keratin extract (K1) of human squamous cell carcinoma and P3X63Ag8/U1 syngeneic myeloma cells. UNME/K1 was purified by a protein-A affinity column and was of the IgG2a type, as determined by immunoelectrophoresis and gel diffusion techniques. When tested against keratins of different types of urinary bladder tumors using enzym linked immunosorbent assay (ELISA), UNME/K1 reacted only with the high molecular weight keratin of squamous cell carcinoma and showed selectivity towards specific histopathological grades of tumors.

Topics: Animals; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Humans; Immunoglobulin G; Keratins; Mice; Schistosomiasis haematobia; Urinary Bladder Neoplasms

Cytokeratin shedding into urine was measured using a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) in 282 individuals. Samples included urine from normal controls, patients with urogenital conditions and bladder cancer patients. A monoclonal antibody prepared against cytokeratins extracted from a hyperkeratotic low grade squamous cell carcinoma (UNME/K1) was used in the assay. The results indicated reasonable levels of sensitivity (83%), specificity (67%) and overall accuracy (70%) in the detection of bladder cancer. The levels of sensitivity in detecting squamous and transitional cell carcinoma patients were 87 and 73% respectively. The low level of specificity was due to a high frequency of false positive results (55%) within the urogenital controls; this suggests that further immunochemical and immunohistopathological analyses of associated urothelial cytokeratins are required.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Enzyme-Linked Immunosorbent Assay; Female; Humans; Keratins; Male; Schistosomiasis haematobia; Sensitivity and Specificity; Urinary Bladder Neoplasms

Cytokeratin shedding into the urine was measured using an enzyme-linked immunosorbent assay in 154 individuals. Samples include urines of normal controls, patients with urological conditions other than bladder cancer and bladder cancer patients. The assay results reflect the potential value of cytokeratin shedding in urine as a new urinary marker for bladder cancer. A 94% sensitivity for patients with squamous cell carcinoma of the bladder suggested the importance of using antibodies prepared against cytokeratin extracted from the same cell type of carcinoma as that to be detected. The relatively low sensitivity shown while detecting transitional cell carcinoma patients and the relatively low degree of assay specificity suggested the use of a panel of monoclonal antibodies specific to various types of cytokeratins of bladder carcinoma.

Topics: Adult; Antibodies, Monoclonal; Antibody Specificity; Biomarkers, Tumor; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Enzyme-Linked Immunosorbent Assay; Female; Humans; Keratins; Male; Middle Aged; Predictive Value of Tests; Schistosomiasis haematobia; Sensitivity and Specificity; Urinary Bladder Neoplasms

Expression of low and high molecular weight cytokeratin proteins was investigated immunohistochemically in a variety of transitional and squamous epithelial lesions of the urinary tract with and without schistosomiasis. The monoclonal antibodies used were CAM 5.2 and NCL5D3 for low, PK 63 and 121 for high, and MAK 6 for a broad range of intermediate molecular weight cytokeratins. On staining with CAM 5.2 and NCL5D3, urothelial hyperplasias (n = 12) and grades 1 (n = 5) and 2 (n = 10) papillary transitional cell carcinomas showed labelling patterns quite distinct from carcinoma in situ (n = 4) and non-papillary grades 2 (n = 6) and 3 tumours (n = 3). Among squamous lesions only focal positivity was obtained in 14 of 22 moderate to poorly differentiated squamous cell carcinomas. By contrast, PK 63 and 121 stained squamous lesions exclusively. MAK 6 stained the whole range of urothelial and squamous lesions with the exception of squamous metaplasias. Polyclonal antikeratin adequately labelled spindle cell areas of high grade tumours. The distinctive staining patterns given by these or similar antibodies may help in the identification of squamous metaplasia and in diagnosing tumours of the urothelium.

Topics: Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Epithelium; Humans; Keratins; Lymphatic Metastasis; Molecular Weight; Schistosomiasis haematobia; Urinary Bladder Neoplasms

Squamous cell carcinomas of the urinary bladder and the epithelial lesions associated with infection by Schistosoma haematobium were histopathologically and immunohistochemically described for keratin proteins (TK, 41-65 kDa; KL1, 55-57 kDa; PKK1, 40, 45 and 52.5 kDa), involucrin, and epithelial membrane antigen (EMA). Normal urothelial epithelium was positive for all keratins, and showed absent or slight reactions for involucrin and EMA in superficial umbrella cells. The intestinal type of epithelium was composed of columnar cells and small basal cells; TK was positive in the basal cells, KL1 staining was positive in the columnar cells, whereas PKK1 was negative or slight in the columnar cells. Involucrin was confined to columnar cells. Squamous metaplastic epithelium showed a rather regional keratin distribution: TK was distributed in all layers, KL1 decorated upper spinous and granular layers, but PKK1 did not bind, and involucrin staining existed only in upper spinous and granular cells. Keratin expression in squamous cell carcinomas indicated heterogeneity and its stainability was dependent on the degree of keratinization: The G 1 type revealed strong reaction, the G 2 type showed a similar distribution pattern, but the staining intensity was less, and the G3 type showed irregular staining with decreased intensity. Involucrin staining was limited to keratinized cells of carcinoma as was that for EMA.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Female; Histocytochemistry; Humans; Immunochemistry; Keratins; Male; Membrane Proteins; Middle Aged; Mucin-1; Protein Precursors; Schistosomiasis haematobia; Urinary Bladder Neoplasms

The monoclonal antibody CAM 5.2 was used to investigate the expression of lower molecular weight cytokeratin proteins immunocytochemically in conventionally processed samples of schistosoma-associated squamous metaplasias and carcinomas of the urinary bladder. The antibody did not differentiate between squamous metaplasias and well differentiated squamous carcinomas, though it did focally label moderate to poorly differentiated tumours. The results suggest that squamous carcinomas of the bladder in this setting differ fundamentally from such tumours at other sites in their patterns of cytokeratin protein expression.

Topics: Antibodies, Monoclonal; Carcinoma, Squamous Cell; Humans; Keratins; Metaplasia; Molecular Weight; Schistosomiasis haematobia; Urinary Bladder; Urinary Bladder Neoplasms