Cases reported "Prostatic Neoplasms"

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1/8. Numerical chromosomal changes in metastatic prostate cancer following anti-androgen therapy: fluorescence in situ hybridization analysis of 5 Japanese cases.

    We used fluorescence in situ hybridization with centromere-specific probes for chromosomes 7, 8, 10, and Y to determine the copy number of these chromosomes in metastatic prostate cancers of five Japanese cases. Freshly prepared samples were obtained from prostate needle biopsies at different phases of clinical treatment; pretreatment, 1 week, 4 weeks, 12 weeks, 24 weeks post-treatment (PT), and clinical relapse. Gain of chromosomes 7 and 8, as noted in pretreatment samples; however, in post-treatment specimens (four of five cases), a remarkable reduction in the number of cells with extra copies of these chromosomes was detected. This decrease in the number of cells with additional chromosome 7 and 8 signals was correlated with the clinicohistopathological findings until 4 weeks PT. chromosomes Y and 10 did not show numerical aberrations before treatment or changes in cells with aneusomy after treatment in all five cases. Our results suggest that gains of chromosomes 7 and 8 correlate with high grade and stage, and that changes in the cell number with aneusomy of chromosomes 7 and 8 reflect the clinical effects of anti-androgen therapy at an early phase, which may also indicate the androgen dependency of prostate cancer cells.
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2/8. fluorescence in situ hybridization to assess transitional changes of aneuploidy for chromosomes 7, 8, 10, 12, 16, X and Y in metastatic prostate cancer following anti-androgen therapy.

    There have been few detailed studies conducted on the cell population in relation to cytogenetic changes between the pre- and post-treatment periods in patients with prostate cancer. We investigated numerical chromosome changes associated with anti-androgen therapy, using fluorescence in situ hybridization (FISH). FISH using chromosome-specific centromeric probes was used to assess transitional changes in the frequency of aneuploidy for chromosomes 7, 8, 10, 12, 16, X, and Y in prostate cancer during the pre- and post-treatment periods. Gains of chromosomes 7, 8 and 12 were notable in the pre-treatment samples (8 out of 9 cases in chromosome 7; 8 out of 9 cases in chromosome 8; 7 out of 9 cases in chromosome 12), while a notable reduction in the number of cells with extra copies of these chromosomes was observed in post-treatment specimens. Other chromosomes did not show noticeable change in their FISH signals at each phase of clinical treatment in all 9 cases. Changes in cell number with high ploidies of chromosome 7, 8 and 12 reflect the clinical effects of anti-androgen therapy at the early phase, which might explain the androgen dependency of metastatic prostate cancer cells.
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3/8. Adenoid cystic carcinoma of the prostate: a case report with immunohistochemical and in situ hybridization staining for prostate-specific antigen.

    A 43-year-old man with urinary outlet obstruction was referred to our hospital. A digital rectal examination revealed an elastic hard prostate. The serum prostate-specific antigen (PSA), serum prostatic acid phosphate and gamma-seminoprotein levels were found to be within the normal range, and transrectal ultrasound sonography provided normal findings. The patient underwent a subcapsular prostatectomy under a diagnosis of benign prostatic hyperplasia. Histopathologically, the lesion was diagnosed as an adenoid cystic carcinoma of the prostate. Because a further examination revealed a pathologic extension into the urinary bladder, a radical cystoprostatectomy was performed. The expression of PSA protein and PSA mRNA was studied by means of immunohistochemistry and an in situ hybridization technique. The adenoid cystic carcinoma in the patient did not show any positive signs for PSA protein or PSA mRNA.
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4/8. Evidence for gains at 15q and 20q in brain metastases of prostate cancer.

    Many detailed genetic studies have been reported on prostate carcinogenesis. A major shortcoming of these studies, however, is the fact that most data have been gained from investigations that were performed at a single point of time during tumor development. Only little is known on the dynamic process of genetic changes during the course of the disease. We performed comparative genomic hybridization in two cases of prostate cancer brain metastases. Tissue samples from the primary tumors, the locally recurrent tumor in one case, and the brain metastases from both cases were available for analysis. The number of chromosome abnormalities was found to be increased in the metastases. This contrasts to a remarkably stable chromosome composition of the primary tumor over several years, even in an androgen-depleted environment. When focusing on these changes, which either emerged as new common aberrations in both brain metastases, or which were commonly present in the primary and metastatic tumors, we were able to delineate five chromosomal sites that are assumed to be related to prostate cancer metastasis: 8q21 approximately q22, 8q24, 15q24 approximately q26, 20q12 approximately q13.1, and Xq12 approximately q21. These findings provide new evidence for a putative role of genes at 15q and 20q in the metastatic process of prostate cancer.
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5/8. Small cell carcinoma of the prostate. A case report.

    A case of small cell carcinoma of the prostate reported here was studied by immunohistochemical and electron microscopic procedures. Most tumour cells were positive for argyrophil (Grimelius) stain and had dense core neurosecretory granules in the cytoplasm. But immunohistochemical staining revealed vasoactive intestinal polypeptide and calcitonin only in a few cells, and it was still obscure what kinds of hormones were produced in this tumour. By dot blot hybridization, our case showed no amplification of myc family gene which is suggested to be associated with a poor clinical outcome in pulmonary small cell carcinoma.
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6/8. A case of therapy-related extramedullary acute promyelocytic leukemia.

    We report a patient with extramedullary acute promyelocytic leukemia (APL) occurring after radiation therapy for carcinoma of the prostate. To the authors' knowledge, this patient represents the first case of cytogenetically and fluorescence in situ hybridization (FISH) confirmed therapy-related extramedullary APL. In contrast to the majority of previously reported t-APL, this case underwent a very unfavorable course.
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7/8. Androgen receptor gene amplification in a recurrent prostate cancer after monotherapy with the nonsteroidal potent antiandrogen Casodex (bicalutamide) with a subsequent favorable response to maximal androgen blockade.

    OBJECTIVE: We recently found amplification of the androgen receptor (AR) gene in approximately 30% of locally recurrent prostate carcinomas from patients treated by conventional androgen deprivation (castration) therapy, whereas none of the untreated primary prostate tumors showed this amplification. This suggests that AR gene amplification was selected during androgen deprivation therapy. The present case study represents our initial approach to evaluate the role that AR amplification may play in therapy resistance after other forms of endocrine therapy. MATERIAL AND methods: Specimens from both a primary and a subsequent locally recurrent tumor were studied for amplification of the AR gene by fluorescence in situ hybridization from a prostate cancer patient who experienced tumor progression after monotherapy with the potent antiandrogen bicalutamide (Casodex, a trade mark, the property of Zeneca Ltd). RESULTS AND CONCLUSIONS: High-level amplification of the AR gene was found in the recurrent tumor, whereas no evidence of amplification was found in the primary tumor. After recurrence, the patient first received chemotherapy (ifosfamide) for 15 weeks with no response, followed by maximal androgen blockade (MAB). The latter therapy resulted in a favorable short-term response. This case study has the following implications which warrant further research: (1) AR amplification may be selected not only by castration but also by therapy with a competitive peripheral androgen-receptor-blocking agent, and (2) recurrent tumors with AR amplification may be particularly likely to benefit from MAB as a second-line therapy.
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8/8. Synovial sarcoma of the prostate with t(X;18)(p11.2;q11.2).

    A case of monophasic synovial sarcoma of the prostate in a 37-year-old man is reported. Histologically, the tumor was chiefly composed of uniform spindle and oval cells, which often formed interlacing fascicles resembling those of fibrosarcoma. In some areas, the compact fascicles of tumor cells alternated with hypocellular myxoid tissue bearing a superficial resemblance to peripheral nerve sheath tumors, whereas small portions of the tumor showed a pericytomatous pattern consisting of polygonal cells arranged around dilated, thin-walled blood vessels. By immunohistochemistry, vimentin was detected in most cells, and a focal reactivity for epithelial membrane antigen was also observed. The tumor cells, however, were negative for keratin, S-100 protein, neuron-specific enolase, CD34, desmin, muscle-specific actin, and alpha-smooth muscle actin. cytogenetic analysis and fluorescence in situ hybridization (FISH) using the cultured tumor cells demonstrated a translocation t(X;18)(p11.2;q11.2), an aberration specific for synovial sarcoma. To the authors' knowledge, this is the first report of a primary prostatic synovial sarcoma confirmed by cytogenetic analysis.
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