Clinical management of incidental prostate cancer (IPC) remains challenging since its clinical course cannot be predicted by conventional histopathology. Aiming to define predictive factors in IPC, we correlated the immunohistochemically detected expression of prostate-specific antigen (PSA), prostatic acid phosphatase (PSAP), alpha-methylacyl-CoA racemase (AMACR, p504s), and androgen receptor in transurethral resection specimens with Gleason scores and histologic staging on the corresponding radicals in a cohort of 54 patients (mean age, 65.9 years; range, 49-80 years). PSAP expression showed a significant correlation with tumor staging (rho = -0.37; p = 0.02) but not with Gleason scores (rho = -0.06; p = 0.69). K-statistics revealed a highly significant moderate interobserver agreement concerning the evaluation of PSAP staining (K = 0.47; p < 0.001). In contrast, the other markers assessed failed to correlate with conventional histopathology. Therefore, PSAP might be predictive of tumor stage in IPC and represent a valuable adjunct for clinical decisions in terms of individual therapeutic management.
"After sipuleucel-T treatment of autologous cells, the product containing increased activated APCs and T cells is reinfused into the patient and contains at least 50 million autologous activated CD54+ dendritic cells, and a variable number of T cells, B cells, natural killer cells, and others . Sipuleucel-T immunotherapy targets cells which express PAP, a secreted glycoprotein enzyme that is expressed in 95% of prostate tissue and PCa; expression levels correlate with tumour staging [38, 39]. Moreover, high serum PAP levels are associated with significantly shorter survival and lower responsiveness to radiation therapy . "
[Show abstract][Hide abstract] ABSTRACT: The mainstay therapeutic strategy for metastatic castrate-resistant prostate cancer (CRPC) continues to be androgen deprivation therapy usually in combination with chemotherapy or androgen receptor targeting therapy in either sequence, or recently approved novel agents such as Radium 223. However, immunotherapy has also emerged as an option for the treatment of this disease following the approval of sipuleucel-T by the FDA in 2010. Immunotherapy is a rational approach for prostate cancer based on a body of evidence suggesting these cancers are inherently immunogenic and, most importantly, that immunological interventions can induce protective antitumour responses. Various forms of immunotherapy are currently being explored clinically, with the most common being cancer vaccines (dendritic-cell, viral, and whole tumour cell-based) and immune checkpoint inhibition. This review will discuss recent clinical developments of immune-based therapies for prostate cancer that have reached the phase III clinical trial stage. A perspective of how immunotherapy could be best employed within current treatment regimes to achieve most clinical benefits is also provided.
BioMed Research International 09/2014; 2014. DOI:10.1155/2014/981434 · 3.17 Impact Factor
"Serum PAP levels are low in healthy individuals and increased levels are associated with PCa. For example, it is shown that PAP is aberrantly expressed in high Gleason score PCa (72, 73). Ozu et al. showed that serum PAP levels, like serum PSA, are significantly increased within the escalating PCa disease stages. "
[Show abstract][Hide abstract] ABSTRACT: Prostate cancer (PCa) is the most common cancer in men and the second most common cause of cancer-related death in men. In recent years, novel therapeutic options for PCa have been developed and studied extensively in clinical trials. Sipuleucel-T is the first cell-based immunotherapeutic vaccine for treatment of cancer. This vaccine consists of autologous mononuclear cells stimulated and loaded with an immunostimulatory fusion protein containing the prostate tumor antigen prostate acid posphatase. The choice of antigen might be key for the efficiency of cell-based immunotherapy. Depending on the treatment strategy, target antigens should be immunogenic, abundantly expressed by tumor cells, and preferably functionally important for the tumor to prevent loss of antigen expression. Autoimmune responses have been reported against several antigens expressed in the prostate, indicating that PCa is a suitable target for immunotherapy. In this review, we will discuss PCa antigens that exhibit immunogenic features and/or have been targeted in immunotherapeutic settings with promising results, and we highlight the hurdles and opportunities for cancer immunotherapy.
Frontiers in Immunology 05/2014; 5:191. DOI:10.3389/fimmu.2014.00191
"Despite the great progress in our understanding of the disease process and standardization of diagnostic criteria for prostate cancer, the majority of prostate tumors are detected at early stages with uncertain prognosis (Larne et al., 2012). Previous studies have shown that PAP can serve as a prostate cancer marker by proportionally increasing secretory PAP expression as prostate cancer progresses (Azumi et al., 1991; Wang et al., 2005; Gunia et al., 2009). High levels of PAP expression were detected in high Gleason score prostate cancers as determined by immunohistochemistry (Gunia et al., 2009). "
[Show abstract][Hide abstract] ABSTRACT: Prostate cancer is one of the most prevalent non-skin related cancers. It is the second leading cause of cancer deaths among males in most Western countries. If prostate cancer is diagnosed in its early stages, there is a higher probability that it will be completely cured. Prostatic acid phosphatase (PAP) is a non-specific phosphomonoesterase synthesized in prostate epithelial cells and its level proportionally increases with prostate cancer progression. PAP was the biochemical diagnostic mainstay for prostate cancer until the introduction of prostate-specific antigen (PSA) which improved the detection of early-stage prostate cancer and largely displaced PAP. Recently, however, there is a renewed interest in PAP because of its usefulness in prognosticating intermediate to high-risk prostate cancers and its success in the immunotherapy of prostate cancer. Although PAP is believed to be a key regulator of prostate cell growth, its exact role in normal prostate as well as detailed molecular mechanism of PAP regulation is still unclear. Here, many different aspects of PAP in prostate cancer are revisited and its emerging roles in other environment are discussed.
Biomolecules and Therapeutics 01/2013; 21(1):10-20. DOI:10.4062/biomolther.2012.095 · 1.73 Impact Factor
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