PHASE II STUDIES OF HYDROXYUREA (NSC-32065) IN ADULTS: UROLOGIC AND GYNECOLOGIC NEOPLASMS.
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Explore the source record for details and available documents.
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The development and progression of human prostate cancer is associated with genetic abnormalities in tumor cells. Inactivation of tumor suppressor genes due to allelic loss is thought to be an important mechanism of gene alteration in prostatic neoplasms. In this study we examined allelic loss on chromosome 8p12-21 in microdissected samples of normal prostatic epithelium, high grade prostatic intraepithelial neoplasia (PIN), and invasive prostate carcinoma from the same patients. Tissue microdissection under direct microscopic visualization procures pure populations of cells of interest, including small lesions such as PIN. Among 30 patients with concomitant cancer and PIN, we found loss of heterozygosity on chromosome 8p12-21 in 63% (34 of 54) of foci of PIN examined and 90.6% (29 of 32) of tumors, suggesting that abnormalities on chromosome 8p12-21 may be important in the early stages of prostatic carcinoma development. Several cases in which multiple foci of PIN from the same patient were sampled showed different patterns of allelic loss. Fifty-five % (16 of 29) of the prostate carcinomas contained a potential precursor PIN focus based on allelic loss pattern. Our results are consistent with the hypothesis that PIN arises multifocally within the prostate gland, and that a subset of these lesions progress to become carcinoma.
OBJECTIVE: Accurate staging of prostatic cancer is important for planning an optimal treatment, such as radical prostatectomy in clinical stage T2. About 40-50% of patients operated for cT2 disease show a pathological stage T3 disease. In a prospective study we analysed accuracy of TRUS and endocoil MRI in a group of patients before radical prostatectomy. MATERIALS AND METHODS: 33 consecutive patients suspicious of prostate neoplasms were studied and staged with TRUS and endocoil MRI before prostatic biopsy and before radical prostatectomy. One urologist trained in TRUS conducted the exam, while one radiologist interpreted the MRI studies in a blind mode. The criteria evaluated were accuracy of global staging, extracapsular extension (ECE) and seminal vesicle invasion (SVI). These results were correlated with the histopathological findings after radical prostatectomy. RESULTS: The histopathological results showed 14 patients (42%) with pT2 disease, 18 patients (54%) with pT3 disease and 1 case (4%) of pT4 disease. TRUS showed a low sensitivity (38%) and a good specificity (78%), with an overall accuracy of 50%; the best result was 96% specificity for SVI. Endocoil MRI showed a good sensitivity (70%) and specificity (76%), with an overall accuracy of 73%. Endocoilc was also useful to stage T1c disease when TRUS is negative. TRUS tends to understage, whereas endocoil MRI over-stages prostate cancer. CONCLUSIONS: TRUS and endocoil MRI may help in decision making about the appropriate treatment of prostatic cancer, even if they have limited current value, due to understaging or overstaging.
Many of the alterations in the insulin-like growth factor (IGF) axis in prostatic disease have been associated with changes in the insulin-like growth factor binding proteins (IGFBPs), a multigene family of proteins that are thought to mediate the action of IGFs on target tissues. IGFBP-related protein 1 (rP1), also known as IGFBP-7 or mac25, is a recently described member of the IGFBP family, the biological function of which has yet to be completely ascertained. In this study, we analyzed the localization of IGFBP-rP1 in prostate cancer and benign prostate tissues using immunohistochemistry and a polyclonal antibody, T1A12, that is specific for IGFBP-rP1. The most intense staining was observed in nerves, whereas smooth muscle cells in the prostate stained weakly. Lymphocytes were always negative. When normal prostatic secretory epithelium was present, staining was usually absent. The lining secretory epithelium stained positively in 0 of 12 (0%) cases of benign prostatic hyperplasia, 57 of 63 (90.5%) primary adenocarcinomas, and 7 of 7 (100%) prostate cancer metastases. Prostatic intraepithelial neoplasia showed a similar pattern of staining to that observed for the invasive tumors. Analysis of Northern blots showed that none of the prostate cancer cell lines (LNCaP, C4, C4-2, C4-2B4, 9069E3, DU145, and PC3) expressed IGFBP-rP1 mRNA. This lack of expression was confirmed by immunohistochemistry of s.c.-generated tumor xenografts of LNCaP and C4-2 and by immunoblot on serum-free-conditioned media from all prostatic cell lines. In contrast to these results, tumor xenografts generated by direct intraosseous injection of LNCaP or C4-2 to bone marrow space resulted in tumors that stained positively for IGFBP-rP1. Our results show that IGFBP-rP1 is expressed in both in situ and invasive prostate neoplasms, but not typically in normal secretory or BPH epithelium; furthermore, the expression of IGFBP-rP1 can be induced in human prostate cancer cell lines in vivo on interaction with an appropriate host environment.
A case of metastatic prostatic adenocarcinoma with concurrent Sertoli cell tumor is presented in an old, miniature Schnauzer dog. The prostatic neoplasm was highly anaplastic and had metastasized widely. Clinical signs were compatible with increased estrogen production. It is interesting to note that the prostatic carcinoma, usually considered to be androgen dependent, developed and metastasized, despite the presence of apparently increased estrogen levels.
The binding of 3H-R 1881 to cytosol prepared from benign and malignant prostatic neoplasms has been investigated. We have demonstrated that high affinity binding of 3H-R 1881 is present in cytosol preparations of benign prostatic hyperplasia, in specimens of prostatic cancer obtained from patients prior to hormonal therapy and in carcinoma of the prostate metastatic to lymph nodes. In addition, high affinity binding was present in all specimens of prostatic cancer from patients who had objective evidence of progressive metastatic disease after an initial response to hormonal therapy. Until greater numbers of patients have been studied the significance of these findings can only be speculative. Because the binding of 3H-R 1881 may measure androgen and progesterone receptors future investigations must include careful steroid specificity studies. Finally, because steroidal hormones exert their major influence within the nucleus of target tissues the measurement of nuclear receptor content may provide a more accurate means to predict the hormonal responsiveness of prostatic cancer.
PURPOSE: We summarize the literature addressing factors that influence treatment decisions made by men with prostate cancer. MATERIALS AND METHODS: A MEDLINE search of the English language literature published between 1969 and 2000, using the combined MESH key words "prostatic neoplasms," "patient participation," "Internet" and "decision making," generated 181 abstracts. Only 23 of these publications addressed factors influencing treatment decisions made by men with prostate cancer. Nine additional relevant studies were identified from references in the original 23 articles. Subsequently a search for the term "prostate cancer" using several popular Internet search engines yielded more than 1 million hits. A further search was performed using the key words "prostate cancer" and "prostate" within on-line archives of the United Kingdom television channels BBC, ITV, and channels 4 and 5, and newspapers The Sun, The Daily Mail, The Observer, The Guardian and The Times. RESULTS: When there is poor quality evidence or little professional consensus to support a particular treatment over another, no clinical guidelines regarding treatment are possible. Patients are faced with a series of options, and the data reveal that the process of choosing between these options is based on input from a large number of sources. These sources differ in the way that benefits of treatment are emphasized over harms and vice versa. We identified little evidence regarding which type of input exerts the greatest influence on patients. It may be that the sources associated with the most bias have the greatest influence. CONCLUSIONS: There is a paucity of information on how patients with prostate cancer use different types of input in the treatment decision making process. The physician, as principal caregiver, still appears to have the most direct influence on patient choice. Just how long this status will continue is uncertain.
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Recent advances in molecular biology have allowed us to understand that it is the accumulation of genetic alterations which leads to each step of tumorigenesis. What the specific alterations may be, however, often varies with each neoplasm. Prostate cancer is somewhat unique in its presentation to the pathologist of a bewildering array of histologies difficult to assign to diagnostic categories and contributing to misinterpretations of underlying molecular events. As with any malignancy, it is of utmost importance to thoroughly analyze and record the genetic aberrations found in prostate cancer with the objective of correlation to the pathology and natural history of the disease. Multiple oncogenes and tumor suppressor genes have been investigated in both clinical and latent cancer using conventional mutational analyses. To probe deeper into these genes and to uncover novel molecular events, genomic tumor DNA were examined using restriction landmark genomic scanning (RLGS), a method which allows the identification and comparison of specific genetic alterations within large segments and multiple samples of DNA at a time. This article reviews what has been identified based on numerous molecular studies, focusing on the genetic alterations peculiar to human prostate cancer.