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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the frequency of mutations in the p53 gene in human prostate cancer. The investigated material consisted of 20 primary-tumor tissue specimens, obtained by transurethral resection and tissue specimens of 15 lymph-node metastases, obtained at total prostatectomy. The applied methods encompassed immunohistochemistry on frozen sections, using the monoclonal antibody PAb 1801, and single-strand conformation polymorphism (SSCP) analysis, after amplification of single exon sequences by PCR, on exons 5 to 8 of the p53 gene. The mutations, leading to aberrantly migrating bands in the PCR-SSCP analysis, were identified by direct sequencing of the PCR product. Immunohistochemical and PCR-SSCP analysis were completely confirmative. In the primary tumors, mutations were found in 10% of the specimens (codons 232 and 273), and in lymph-node metastases in 15% of the specimens (codons 248 and 273). In one case (codon 273), the same mutation was found both in the primary tumor and in the lymph-node metastasis. Our results show that p53 mutations are infrequent in both primary and metastatic prostate tumors. In addition, they indicate that there is no strict correlation between p53 mutation and tumor metastasis.
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PMID:Frequency and characterization of p53 mutations in primary and metastatic human prostate cancer. 831 37

We studied 98 patients with locally confined but lymph node positive prostatic cancer (1 stage T1, 29 stage T2, 55 stage T3 and 2 stage T4) who were not treated by radical prostatectomy. A retrospective analysis was done of deoxyribonucleic acid (DNA) ploidy of pretreatment core biopsies of the primary tumor and lymph node metastases. While DNA ploidy has been shown to be an important prognostic factor if applied to radical prostatectomy specimens, core biopsy specimens and nodal metastases have rarely been studied. Of the 98 patients 87 were evaluable for DNA ploidy: 45 (52%) had diploid, 13 (15%) had tetraploid and 29 (33%) had aneuploid tumors. The ploidy of the primary tumor and of the lymph node metastases correlated significantly with the rate of progression and interval to progression. Also, significant correlations were noted between the percentages of cells in the S phase or S plus G2 phases of the cell cycle and interval to progression. Most patients in this study are part of the European Organization for Research and Treatment of Cancer protocol 30846, a prospective randomized study of early versus delayed treatment in lymph node positive, otherwise locally confined prostate cancer. This study is ongoing. Early endocrine treatment was associated with a significantly longer interval to progression. In a Cox regression analysis of the prognostic factors involved in this study, early endocrine treatment was more important than ploidy or proliferation patterns. Stage (T category) and histopathological grade did not show a correlation with progression. Followup is still too short and the numbers of patients are too small for relevant subgroup analysis. DNA ploidy measurement by flow cytometry on archival (paraffin embedded) core biopsy and lymph node material is possible, and produces meaningful results in predicting the prognosis of prostatic cancer. Since this information can be made available before treatment decisions, its exact value in the management of locally confined prostate cancer can be determined.
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PMID:Deoxyribonucleic acid ploidy of core biopsies and metastatic lymph nodes of prostate cancer patients: impact on time to progression. The European Organization for Research and Treatment of Cancer Genitourinary Group. 832 63

There is increasing evidence that nuclear DNA content has significant prognostic value for adenocarcinoma of the prostate. There also appear to be considerable differences in cellular DNA content between patient cohorts when primary tumor or pelvic lymph node metastases are measured. In addition, prostate adenocarcinoma is heterogeneous in DNA measurements; that adds confusion to studies incorporating fine needle aspiration biopsy samples. We compared cellular DNA content in 34 patients with available needle biopsies and pelvic lymph node metastases. Four groups of patients were identified: diploid-range primaries and metastases (8 patients), diploid-range primaries and aneuploid metastases (13), aneuploid primaries and metastases (10), and aneuploid primaries and diploid-range metastases (2). Patients with diploid-range primary tumors had a longer interval to progression and death than did patients with aneuploid primary tumors, although neither was significant in this small series. Patients with diploid-range lymph node metastasis had a longer interval to progression (P = .04) and survival (P = .09) than did individuals with aneuploid metastases. We conclude that the cellular DNA content of prostate cancer metastases in this series of stage D1 patients was more powerful in predicting time to progression and ultimate survival than evaluation of needle biopsy specimens of the primary cancer.
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PMID:Comparison of DNA content in primary and lymph node metastases in prostate adenocarcinoma. 834 55

To date androgen receptor (AR) expression and structure in human prostatic cancer have been studied in primary tumor specimens and in cell lines. Investigation of alterations in the androgen-signalling transduction cascade in prostatic carcinoma metastases is important to improve our understanding of tumor progression towards androgen insensitivity. In the present study we have collected data comparing AR expression in both the primary tumors and the respective pelvic lymph node metastases. Formalin-fixed and paraffin-embedded tissues derived from the primary tumors and positive lymph nodes of 12 patients undergoing radical prostatectomy were immunostained for the AR and prostate-specific antigen (PSA). AR expression was evaluated with the polyclonal antibody PG-21, which is directed against amino acid 1-21 in the N-terminal region of the AR. All primary tumors stained for the AR. In 8 of the 12 lymph nodes examined more than 50% of the tumor cells were AR positive and displayed a uniform staining pattern; in one lymph node metastasis remarkable heterogeneity in AR expression was observed. In two cases less than 10% of the tumor cells stained for the AR. In one case the lymph node metastasis was immunohistochemically negative for the AR, whereas the primary tumor obtained from the same patient displayed intense staining for the AR. PSA was expressed in all metastases and primary tumors. Our data demonstrate that loss of the AR in lymph node metastases from prostatic carcinoma is a rare event.
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PMID:Androgen receptor status of lymph node metastases from prostate cancer. 860 94

Short- and long-term results of stage-III and -IV prostatic cancer treatment were compared in 147 patients without distant metastases. 38 patients were exposed to radiation, 109 patients underwent radiation treatment and local microwave hyperthermia. The response of the primary tumor was evaluated at palpation, ultrasonic investigation and computed tomography. Adjuvant local hyperthermia enhanced antitumor activity of the treatment raising the rate of a complete response from 69% on radiotherapy alone to 94% on thermoradiotherapy, 5-year survival in prostatic cancer stage III and IV increased also from 48 to 65%.
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PMID:[The comparative efficacy of radiation and thermoradiation treatments in prostatic cancer]. 865 38

The dynamic evaluation of tumor markers is a promising area of investigation which is expected to provide clinical information when serial samples are available from the same patient. This is feasible in the post-operatory evaluation, during the follow-up after the treatment for to the primary tumor and in the monitoring of the treatment for metastatic disease. Variations among serial samples may be assessed using both empirical and mathematical approaches. Empirical approaches rely on overcoming a given percentage usually chosen on the base of arbitrary decisions. Mathematical approaches include the actual half-life, the doubling time, a dose/time regression analysis and the calculation of the critical difference. The two former are currently used in clinical practice whereas the two latter are still matter of investigation. As concerns the assessment of the radicality of the surgery for the primary tumor, the serum markers are used in germ cell tumors and in prostate cancer. The half-life of the markers is the decision criteria used in germ cell cancers, while in prostate cancer PSA is expected to be undetectable more than 30 days after the radical prostatectomy. Tumor markers are currently used during the follow-up of several malignancies after the treatment for primary tumor. Although several samples are available, decision criteria are still based on positive/negative cut-off values in several instances. Promising dynamic approaches are under investigation and are expected to lead to earlier and probably more accurate information concerning the disease progression. A critical point still under debate is the actual impact of tumor markers on patients' survival in malignancies incurable when metastatic, such as colorectal cancer and breast cancer. This matter urgently demands perspective clinical studies. Finally, the dynamic use of tumor markers is now commonly applied in the monitoring of the therapy for metastatic malignancies. In this clinical setting mathematical criteria are used for ovarian and and germ cell tumors with promising results. Nevertheless, the use of empirical criteria, namely the percentage of variation between two consecutive samples, is successfully used for the monitoring of the therapy of metastatic breast cancer. In conclusion, when several samples are available from an individual patient they may be evaluated according to dynamic criteria instead of referring to a conventional positive/negative cut-off point. Although mathematical decision criteria are expected to provide more reliable data, empirical approaches are used as well and provide useful information in decision making.
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PMID:Dynamic use of tumor markers, rationale-clinical applications and pitfalls. 869 56

Prostatic carcinoma often shows different behavior in the primary site than in the metastases after endocrine treatment. The pattern of disease progression was evaluated in prostate cancer patients. Two hundred and sixty consecutive patients were observed following the initiation of endocrine treatment (11 patients with stage T1 disease, 42 with stage T2 70 with stage T3, 11 with N + M0 and 126 with stage M1 disease). Of the 117 patients whose disease progressed, 100 could be evaluated in terms of the pattern of disease progression. Twenty-two (64.7%) of the 34 patients with stage T1-3N0M0 showed a pattern of local progression. On the other hand, 56 (84.8%) of the 66 patients with stage N + or M1 experienced a pattern of distant progression. Patients with only distant progression numbered 36 cases and patients with local progression and distant progression numbered 20 cases. Most of the distant progressions appeared in bone site. Local progression was observed in only 30 (45.5%) patients with stage N + or M1 disease. In patients with localized disease (T1-3N0M0), both the interval to disease progression and the time to cancer death from the start of disease progression were significantly longer than those of patients with stage N + or M1. However, once bone metastasis occurred, the disease tended to progress rapidly. There was no significant difference between the interval to cancer death after the appearance of bone metastasis in patients with initially localized stages (T1-3N0M0) and the time to cancer death after disease progression in patients with metastatic disease (N + or M1). The study shows a heterogenous behavior of the prostatic tumor after endocrine treatment. This suggests that metastases and primary tumor have different clonal compositions. The study also supports the idea that there is a preferential environment for the growth of prostatic carcinoma cells in bone sites.
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PMID:A heterogeneous pattern of progression in endocrine-treated patients with prostate cancer. 874 19

Recently, we demonstrated that an immunoglobulin-like cell adhesion molecule, C-CAM, acts as a tumor suppressor in prostate cancer. It is known that C-CAM is expressed in many epithelial cell types. In this study, we tested the possibility that C-CAM may also suppress bladder cancer progression. We used an orthotopic tumor model, which provides a relevant organ condition for examining the interaction between primary tumor cells and their microenvironment; this interaction has a critical impact on the behavior of carcinoma. We constructed a recombinant adenovirus expressing C-CAM1 (an isoform of C-CAM) and infected the 253J B-V cell line, a tumorigenic human bladder carcinoma subline. In vitro, C-CAM1 protein was detected in C-CAM1 adenovirus-infected cells but not in antisense control virus-infected cells, and the levels of expression showed dose dependency. When these cells were injected orthotopically in nude mice, we found that the increased expression of C-CAM1 in the 253J B-V cells repressed the growth of 253J B-V-induced tumors. Taken together, these data indicate that C-CAM1 is a potent tumor suppressor in human bladder cancer.
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PMID:Suppression of human bladder cancer growth by increased expression of C-CAM1 gene in an orthotopic model. 875 7

Tumor progression to the stage of metastasis may result in part from the selection of certain primary tumor cell clones which are phenotypically competent for survival, invasion, and growth at secondary sites. Selection for traits such as loss of growth inhibitory responses, acquisition of increased adhesiveness, increased local immunosuppression, and enhanced motility and collagenase activities likely contribute to cancer progression and may be regulated through the action of growth factors. The transforming growth factors (TGF-beta) family of growth factors has often been associated with these traits and tumor progression; therefore, elimination or subversion of TGF-beta-responsive pathways should be considered as a mechanistic framework for metastatic events. In this report, we have compared growth and extracellular matrix responses to TGF-beta in six metastatic and six primary tumor-derived cell lines in a mouse model of prostate cancer. We have found that tumor cell lines derived from focal pulmonary metastasis secreted relatively greater quantities of total TGF-betas, lost most or all TGF-beta1 growth inhibition, but responded to TGF-beta1 through induction of the type IV collagenase matrix metalloproteinase-9, whereas cell lines derived from tumors which proliferated at the primary site retained the growth inhibition but lacked collagenase activity. Synthesis of another extracellular matrix protein, plasminogen activator inhibitor 1, was stimulated by TGF-beta1 in both primary as well as metastatic tumors. These results suggest that acquisition of differential responses to the TGF-beta family could result in phenotypic traits which facilitate tumor metastasis from certain primary site clones.
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PMID:Transforming growth factor beta1 stimulates contrasting responses in metastatic versus primary mouse prostate cancer-derived cell lines in vitro. 876 34

This report describes the prognostic value of computerized nuclear texture analysis in metastatic prostate cancer. Seventy-seven patients with histologically verified prostate carcinomas and skeletal metastases were selected from a Scandinavian multicenter study (SPCG-2). Thirty-six therapy-resistant patients experienced objective progression and cancer-related death within 2 years after orchiectomy. Thirty patients responded well to orchiectomy, i.e., showed objective disease remission and no signs of progression during 3 years of follow-up. From this data set, 10 randomly chosen therapy-resistant and 10 randomly chosen therapy-sensitive carcinomas were used in our previous study to find the optimal combination of features that can discriminate between the two groups (Yogesan et al.: Cytometry 24:268-276, 1996). In addition to these two groups, 11 patients experienced stable disease or disease remission during the first year and a secondary progression during the second or third year of follow-up, with subsequent cancer-related death. Traditional clinical prognostic factors such as histopathological grading and serum markers could not discriminate between these groups of patients. Therefore, image analysis techniques based on texture analysis have been utilized in this study of prognosis of prostate cancer. Feulgen-stained monolayers of nuclei were prepared from paraffin-embedded material taken from the primary tumor before endocrine ablation. Four different textural features were selected from the training data set to calculate the discriminating function. This function separated the therapy-sensitive and the therapy-resistant patients with 87% accuracy in the independent data set. This study demonstrates that it is possible to predict tumor progression and survival for endocrine-ablated metastatic prostate carcinomas using computerized nuclear texture analysis on light microscopy images from prostate biopsies taken at the time of diagnosis.
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PMID:Nuclear texture analysis: a new prognostic tool in metastatic prostate cancer. 880 May 61


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