ABSTRACT Prostatic adenocarcinoma with neuroendocrine differentiation of the Small Cell type. Adenocar- cinomas (AC) account for more than 90% of the prostatic malignant neoplasias; a neuroendocrine differentiation (NE) component is to be considered in cases of atypical evolution for its diagnostic and therapeutic relevance. The (NE) originates by proliferation of the NE cells of the acinar epithelium and may develop into two different histologic patterns, a "Carcinoid" type and a "Small Cell" type. We report a patient with a prostatic AC diagnosed 5 years before his death with worsening of the disease together with a return of the prostatic specific antigen (PSA) to normal values and the presence of hepatic metastases of a tumor (NE) of the small cell type. The autopsy confirmed the presence of a prostatic tumor with areas of (AC) type and (NE) small cell type and multiple hepatic metastases (NE).

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Only a few markers have been instrumental in the diagnosis of cancer. In contrast, tumor markers play a critical role in the monitoring of patients. The patient's clinical status and response to treatment can be evaluated rapidly using the tumor marker half-life (t(1/2)) and the tumor marker doubling time (DT). This report reviews the interest of determining these kinetic parameters for prostate-specific antigen, human chorionic gonadotropin, alpha-fetoprotein, carcinoembryonic antigen, cancer antigen (CA) 125, and CA 15-3. A rise in tumor markers (DT) is a yardstick with which benign diseases can be distinguished from metastatic disease, and the DT can be used to assess the efficacy of treatments. A decline in the tumor marker concentration (t(1/2)) is a predictor of possible residual disease if the timing of blood sampling is soon after therapy. The discrepancies in results obtained by different groups may be attributable to the multiplicity of immunoassays, the intrinsic characteristics of each marker (e.g., antigen specificity, molecular heterogeneity, and associated forms), individual factors (e.g., nonspecific increases and renal and hepatic diseases) and methods used to calculate kinetics (e.g., exponential models and timing of blood sampling). This kinetic approach could be of interest to optimize patient management.
    Clinical Chemistry 11/1999; 45(10):1695-707. · 7.15 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Neuroendocrine (NE) cells occur as scattered foci within prostatic adenocarcinoma, similar to their distribution within ductal epithelial cells of the normal prostate. However, the density of NE cells is often greater in prostate carcinomas than in normal tissue, and the frequency of NE cells correlates with tumor grade, loss of androgen sensitivity, autocrine/paracrine activity, and poor prognosis. Although NE cells are nonmitotic, proliferating cells are found in direct proximity to them, suggesting that NE cells provide paracrine stimuli for surrounding carcinoma cells. In vitro, differentiation of the LNCaP and PC3M prostatic tumor cell lines to a NE phenotype can be induced by dibutyryl cyclic AMP (cAMP), suggesting that physiological agents that increase intracellular concentrations of cAMP might regulate NE differentiation in vivo. Indeed, we demonstrate in this report that LNCaP cells acquire NE characteristics in response to treatment with physiological and pharmacological agents that elevate intracellular cAMP, agents such as epinephrine, isoproterenol, forskolin, and dibutyryl cAMP. The androgen-independent LNCaP-derived cell line C4-2 also responded to these agents, indicating that cells representing later stages of tumor progression are also capable of differentiation. The NE phenotype in this study was monitored by the appearance of dense core granules in the cytoplasm, the extension of neuron-like processes, loss of mitogenic activity, and expression of the NE markers neuron-specific enolase, parathyroid hormone-related peptide, neurotensin, serotonin, and chromogranin A. However, contrary to previous reports, we observed rapid loss of the NE phenotype in both LNCaP and C4-2 cells upon withdrawal of inducing agents. Withdrawal also resulted in a rapid, dramatic increase in tyrosine kinase and mitogen-activated protein kinase activities, suggesting that activation of these intracellular signaling enzymes may be important for reentry into the cell cycle. Together, these results indicate that chronic cAMP-mediated signaling is required to block proliferation of prostate tumor cells and to induce NE differentiation.
    Cancer Research 09/1999; 59(15):3821-30. · 8.65 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Clinical information and histological slides of 20 cases of small cell carcinoma of the prostate seen at The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston over a 23-year period were reviewed. Patient's ages ranged from 30 to 89 years (median, 67 years). In nine cases, pure adenocarcinoma of the prostate preceded recognition of the small cell component by 7 months to 8 years (median, 18 months); five of these were initially at Stage A. There was a small cell component at presentation in 11 cases (10, Stage D). Small cell carcinoma was merging with the adenocarcinoma in 11 cases and represented 30% to 90% of total tumor volume. Eleven of 20 patients died of their disease. Those presenting initially with a pure adenocarcinoma survived between 7 months and 9 years (median, 24 months). After the recognition of the small cell carcinoma component, regardless of a prior history of adenocarcinoma, death followed within 1.5 years (median, 5 months). This study suggests a biologic difference in behavior in prostatic carcinoma containing a small cell carcinoma component. The small cell component may manifest early or late in the disease.
    Cancer 06/1987; 59(10):1803-9. · 5.20 Impact Factor

Full-text (2 Sources)

Available from
Oct 16, 2014