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1/7. Molecular cytogenetic identification of cyclin d1 gene amplification in a renal pelvic tumor attributed to phenacetin abuse.

    Despite extensive epidemiologic evidence of phenacetin abuse as a risk factor for renal pelvic carcinomas, genetic alterations in the resultant tumors remain largely unclear. In this report, a phenacetin-associated renal pelvic carcinoma (histologically a transitional-cell carcinoma) from an 80-year-old female patient was evaluated by molecular cytogenetic methods. fluorescence in situ hybridization was used to identify chromosome gains or losses for the cyclin d1, p53, Rb and c-myc genes and the ploidy of their respective chromosomes. cyclin d1 gene amplification, but normal copy numbers of p53, Rb and c-myc, and normal ploidy of chromosomes 8, 11, 13 and 17 were observed. Expression of cyclin d1 protein was confirmed by immunohistochemistry. In the absence of p53, Rb or c-myc abnormalities, the results suggested that cyclin d1 gene amplification and its protein overexpression may be involved in the genesis of renal pelvic carcinomas associated with phenacetin abuse.
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2/7. Basaloid carcinoma of the colon arising at the splenic flexure.

    AIMS: Basaloid carcinomas typically arise in the anal canal and there are only three well-documented cases of this neoplasm reported outside the anal canal, none more proximally than the sigmoid colon. The first occurrence of a basaloid colonic carcinoma arising outside the sigmoid colon, at the splenic flexure, is presented. methods AND RESULTS: A splenic flexure mass was resected from a 54-year-old man with a 3-week history of abdominal discomfort, diarrhoea and weight loss. This tumour, like typical anal canal basaloid carcinomas, was composed of islands of basaloid cells with peripheral nuclear palisading; within many islands there was central necrosis and focal squamous differentiation. Ultrastructural and immunohistochemical studies confirmed the basaloid nature and focal squamous differentiation within this neoplasm. Basaloid carcinoma of the anal canal has been associated with human papilloma virus. Using in-situ hybridization, HPV dna was not detected in this case. CONCLUSIONS: Outside the anal canal, it has been postulated that basaloid colonic carcinomas may arise from cloacogenic embryologic rests, squamous metaplastic epithelium, or totipotential basal cells. The location and pathological findings of this tumour suggest that this rare colonic neoplasm arises from a totipotential basal cell.
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3/7. Immunohistomorphologic and molecular cytogenetic analysis of a carcinosarcoma of the urinary bladder.

    Carcinosarcomas of the urinary bladder are malignant biphasic tumors with an epithelial and a spindle cell component. For the histogenesis of the two components, a biclonal and a monoclonal origin are discussed. We present the immunomorphology and molecular cytogenetics of such a case. The immunohistology of biopsies of the urinary bladder revealed a poorly differentiated urothelial carcinoma (GIII) and a co-existing pleomorphic, spindle cell leiomyosarcoma (GIII). The two components were microdissected and further analyzed for gains and losses of chromosomal material using comparative genomic hybridization. In addition, loss of heterozygosity analyses were included. The tumor components revealed as overlapping core aberrations losses on the short arm of chromosome 9 and on the long arm of chromosome 11. However, both components showed additional aberrations exclusively detected in one of the components. The occurrence of overlapping aberrations strongly argues for a monoclonal origin of this tumor with a common ancestor. The additional aberrations of the components point to an independent and divergent course of tumor progression in both components.
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4/7. Triple cancers in the urogenital area of a patient with aplastic anemia.

    Three epithelial neoplastic lesions, perineal Bowenoid papulosis, uterine cervical carcinoma, and bladder transitional cell carcinoma, which occurred in a mildly immunosuppressed patient who had aplastic anemia were studied for human papillomavirus (HPV) infection. In the Bowenoid papulosis, HPV type 16 dna was identified by polymerase chain reaction (PCR) and by in situ hybridization (ISH). In contrast, in the uterine cervical carcinoma, HPV 16 was not detected, although possibly another unidentified type of HPV in the lesion was suggested by the ISH findings. In the bladder transitional cell carcinoma, neither papillomavirus genus-specific (PGS) antigen nor HPV dna was found.
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5/7. A case of granulomatous hepatitis after intravesical bacillus Calmette-Guerin administration.

    A 61-year-old man received intravesical bacillus Calmette-Guerin (BCG) as treatment for superficial bladder carcinoma. High spiking relapsing fevers began 39 days after the initial treatment. A liver biopsy revealed noncaseating granuloma. Deoxyribonucleic acid hybridization of the bone marrow was positive for mycobacterium tuberculosis complex. pressure exerted to instill the BCG may have favored dissemination.
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6/7. Presence of human papillomavirus type 16 genome in bladder carcinoma in situ of a patient with mild immunodeficiency.

    Using blot hybridization, we analyzed 10 bladder tumors (1 transitional cell carcinoma in situ, 1 adenocarcinoma, and 8 papillary tumors) for the presence of human papillomavirus (HPV) dna. We detected HPV 16 dna in a transitional cell carcinoma in situ, whereas no HPV dna was found in the other bladder tumors. The patient, a 40-year-old female, who harbored HPV 16 dna in the bladder tumor, had mild immunodeficiency and recently suffered from the bladder tumor, common warts on the right hand, bowen's disease of the vulva, and severe dysplasia of the vaginal wall. From each of these lesions, we detected the dna of HPV 16 or an unclassified HPV. HPV DNAs existed in nonintegrated form in all lesions examined. To our knowledge, this is the first case in which a bladder tumor was shown to harbor HPV dna. However, HPV does not seem to be regularly present in bladder tumor, because we could not detect HPV dna from the most common bladder tumor, i.e., papillary tumor. Our demonstration of HPV 16 dna in a transitional cell carcinoma in situ of the bladder suggests that HPV may be associated with some of the bladder tumors of this type.
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7/7. karyotype and FISH analysis of a newly established cell line derived from a human bladder carcinoma.

    A new human malignant urologic cell line was established in vitro from a moderately differentiated transitional cell carcinoma of the bladder and cytogenetically characterized. Repeated chromosome analyses of the cell line using conventional RHG and GTG banding and non-radioactive in situ hybridization showed a stable karyotype with a modal number of 48 and chromosomal rearrangements, some of which have not been previously described. Numerical deviation included three trisomies ( 7, 8, 9) and one nullisomy (-19, -19). Structural changes involved a balanced translocation (1;5)(q12;q12), an isochromosome 3q, a 14p , and two markers. fluorescence in situ hybridization (FISH), using biotin-labeled alpha satellite probes for chromosome 9 or painting for chromosomes 1 and 8, applied to interphase nuclei or metaphases showed similar results to those found by conventional cytogenetic study. This cell line may be an interesting model for fuller characterization by molecular biology studies and for testing anti-cancer drugs in vitro.
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