Biological Features Of Prostate Cancer Research Articles

MR-Guided Hypofractionated Radiotherapy: Current Emerging Data and Promising Perspectives for Localized Prostate Cancer.

Simple SummaryThe biological features of prostate cancer as a tumor with a low alpha beta ratio have led clinicians to consider the use of higher doses per fraction, thus gaining an advantage both in terms of clinical outcomes and of logistic opportunities. To date, moderate hypofractionated schedules are supported by several international clinical guidelines. The subsequent step was represented by the adoption of extreme hypofractionated schedules, for which recent literature data report non-inferiority results for the five-fractions regimens. In this scenario, the recent introduction of MR-guided daily adaptive radiotherapy is a potential paradigm shift, given the ability to increase the resolution of the pelvis anatomy and to take into account of the daily variations in shape and size of the nearby healthy structures.In this review we summarize the currently available evidence about the role of hybrid machines for MR-guided radiotherapy for prostate stereotactic body radiotherapy. Given the novelty of this technology, to date few data are accessible, but they all report very promising results in terms of tolerability and preliminary clinical outcomes. Most of the studies highlight the favorable impact of on-board magnetic resonance imaging as a means to improve target and organs at risk identification with a consequent advantage in terms of dosimetric results, which is expected to relate to a more favorable toxicity pattern. Still, the longer treatment time per session may potentially affect the patient’s compliance to the treatment, although first quality of life assessment studies have reported substantial tolerability and no major impact on quality of life. Finally, in this review we hypothesize some future scenarios of further investigation, based on the possibility to explore the superior anatomy visualization and the role of daily adapted treatments provided by hybrid MR-Linacs.

NANOG as prognostic factor of prostate cancer course.

To investigate the level of NANOG mRNA in tumor tissue of patients with PC and to analyze the possibility of its use as a marker of the disease course. The study involved 85patients with PC of stages II-IV. Morphological and immunohistochemical studies were performed on serial paraffin sections of resected PC using monoclonal antibodies to Ki-67and androgen receptor. NANOG and miR-214mRNA expression in tumor cells was analyzed by real-time reverse transcription polymerase chain reaction. The identification of CSCs was performed by double-labeled immunohistochemical method using primary antibodies to CD24and CD44. We have revealed notable variability of NANOG mRNA levels in tumor tissue of patients with PC (mean 4.18 ± 0.65a.u. with individual deviations from 0.11 ± 0.03a.u. to 15.24 ± 0.36a.u.). According to NANOG mRNA levels, two groups of the PC patients were delineated: group 1and group 2, with the average NANOG mRNA levels of 2.12 ± 0.16a.u., and 8.68 ± 1.24a.u., respectively. The NANOG mRNA levels in tumor tissue of PC patients of groups 1and 2correlated with preoperative serum prostate-specific antigen level (r = 0.58; p < 0.05and r = 0.64;p < 0.05, respectively), tumor volume (r=0.42; p <0.05and r = 0.72; p < 0.05, respectively), regional lymph node metastases (r = 0.70; p < 0.05and r = 0.75; p < 0.05, respectively). High NANOG mRNA levels in tumor cells were associated with such molecular and biological features of PC as androgen receptor expression (r = 0.52; p < 0.05), high proliferative activity (r = 0.60; p < 0.05) and the presence of CSC markers (r = 0.75; p < 0.05). The findings indicate that NANOG is involved in the formation of the PC malignancy and should be further studied as a potential marker for the prediction of the disease course.

Positron emission tomography (PET) in primary prostate cancer staging and risk assessment

Prostate cancer (PCa) is one of the few neoplasms that are not well served by 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET). As a result, a number of PET tracers have been developed to target particular biological features of PCa. Such agents can be used for diagnosis, staging, identification of biochemical recurrence (BCR) and evaluation of metastatic disease. Here, we focus on primary disease and local staging. To date, magnetic resonance imaging (MRI) has proven superior to PET in the imaging of primary PCa. However, some PET agents have shown remarkable promise in staging high-risk PCa (defined as any combination of a clinical T3, a PSA score >20 ng/mL, or a Gleason score of 8–10), as well as biochemical relapse after definitive therapy and metastatic PCa. PET agents can be divided into those that interrogate tumor metabolism (18F-FDG, 11C-Choline, 18F-Choline, 11C-Acetate, 18F-FACBC), hormone receptors (18F-FDHT), and other targets such as prostate specific membrane antigen (PSMA) (68Ga-PSMA, 18F-DCFBC, 18F-DCFPyl) or gastric releasing peptide (18F-GRP or 18F-Bombesin). In this review, we compare the available PCa targeted PET tracers utilized in staging of high risk tumors.

Apparent diffusion coefficient value as a biomarker reflecting morphological and biological features of prostate cancer

To assess whether there is an association between the apparent diffusion coefficient (ADC) value and the pathological characteristics of prostate cancer. The study cohort consisted of 29 consecutive patients with prostate cancer treated with radical prostatectomy. All patients underwent diffusion-weighted MRI before the prostate biopsy. In 42 tumor foci, the associations of the ADC values with the clinicopathological characteristics and Ki-67 labeling index (LI) were analyzed. High-grade cancers (Gleason score [GS] ≥ 4 + 3), larger cancers (maximum diameter (MD) ≥ 16 mm), and highly proliferating cancers (Ki-67 LI ≥ 4.43 %) had significantly lower ADC values, respectively (P < .001, P = .008, and P = .044, respectively). There was no significant difference in ADC value according to age, prostate-specific antigen, presence of extra-prostatic extension, and intra-tumoral stroma proportion. Multivariate analysis showed that GS, Ki-67 LI, and MD had independent and significant correlations with ADC value (P < .001, P = .006, and P = .002, respectively). Low ADC tumors (<0.52 × 10(-3) mm(2)/s) are likely to be high-grade cancer foci compared with high ADC tumors (relative risk: 65.2). The sensitivity and specificity of the ADC value to predict high-grade cancer foci are 81.8 and 93.5 %, respectively. A low ADC value reflects the morphological and biological features of prostate cancer. Analyzing the ADC value may make it possible to more precisely predict the cancer aggressiveness of each focus before treatment.

A comparison of the biological features of prostate cancer with (PSA+,PSMA+) profile according to RKIP

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A Comparison of the Biological Features of Prostate Cancer with (PSA+, PSMA+) Profile according to RKIP

Purpose. To investigate differences in the biological features of the most immunoexpressed prostate cancer (PC) profiles (PSA+, PSMA+) according to the RKIP. Methods. 19 PC with dominant Gleason grade ≥8 were studied. Expression of PSA, PSMA, RKIP, Raf-1, MEK-1, ERK-1, ERK-2, p-Akt (T308), p-Akt (S473), NF-κB p50, and NF-κBp65 were detected immunohistochemically. Results. Loss of RKIP in the most immunoexpressed PC (PSA+, PSMA+) profile was associated with increased levels of PSA and PSMA expression. Intensities of immunoreactions to PSA and PSMA were higher in cancer cells negative for RKIP (12.51 ± 1.6 and 34.95 ± 1.92) compared to those positive for RKIP (4.68 ± 1.11 and 28.56 ± 0.91). In parallel, missing RKIP expression in PC patients with PSA+, PSMA+ profile was connected with increased components of both Raf-1/MEK/ERK and NF-κB (p65/p50), whereas Akt is activated independently of RKIP. Conclusions. Although characterized by the same (PSA+, PSMA+) profile, PC phenotype missing the RKIP related to invasive potential and greater biological aggressiveness reflected in overexpression of components of Raf-1/MEK/ERK and NF-κB (p65/p50) in which Akt is activated independently of RKIP. Taking into account the PC phenotypes according to RKIP among PSA-PSMA profiles may improve distinguishing them from cancers that will become more aggressive and therefore adapt the therapeutic strategies in those patients.

Overexpression of ETS-1 is associated with malignant biological features of prostate cancer

E26 transformation-specific-1 (ETS-1), an ETS family transcription factor, has been reported to play an important role in a variety of physiological and pathological processes, but clinical implications of ETS-1 expression in prostate cancer (PCa), particularly high-risk cases, including response to androgen-deprivation therapy (ADT) have yet to be elucidated. We examined the expression of ETS-1 using immunohistochemical staining of paraffin-embedded prostate carcinoma tissue obtained by needle biopsy from 69 mostly advanced PCa patients. ETS-1 expression was compared with the clinicopathological characteristics of the 69 patients, including 25 who underwent ADT as a primary treatment. As a result, PCa patients with higher expression of ETS-1 were significantly more likely to be of high stage and high Gleason score (P<0.05). There was no significant association between ETS-1 expression and the initial prostate-specific antigen (PSA) level. In the 25 patients treated by ADT, the staining score for ETS-1 was significantly associated with rapid development of castration-resistant disease within 24 months (P<0.05), whereas the Gleason score and PSA level were not. In conclusion, increased ETS-1 expression was associated with a higher stage, higher Gleason score and shorter time to castration-resistant progression. These data suggest that immunostaining for ETS-1 could be a molecular marker for predicting a poor clinical outcome for PCa patients, particularly those with high-risk disease.

Prognostic prediction following radical prostatectomy for prostate cancer using conventional as well as molecular biological approaches

Although radical prostatectomy has been the mainstay of treatment for men with clinically organ-confined prostate cancer, a certain proportion of men undergoing radical prostatectomy fail to achieve a complete cure of this disease; that is, postoperative biochemical recurrence develops in approximately 30% of men, some of whom will ultimately die of disease progression. A number of studies, therefore, have been carried out to identify factors reflecting prognostic outcomes following radical prostatectomy, which would be potentially helpful for properly counseling individual patients undergoing this surgery. Furthermore, various types of model systems using multiple clinicopathological parameters, such as the nomogram, look-up table and artificial neural network, have been shown to have better performance in postoperative prognostic prediction than the opinions of expert clinicians. However, there have not been any standard models uniformly applied to postoperative prognostic prediction, which could be explained, at least in part, by the use of conventional clinicopathological parameters alone, suggesting the need for the additional evaluation of molecular markers simultaneously considering the unique biological features of prostate cancer. In this review, a search of the literature was carried out focusing on the significance of prognostic models following radical prostatectomy, and it is suggested that these models could be promising tools to provide accurate information on the postoperative clinical course of prostate cancer patients. To widely introduce such models into clinical practice, it is necessary to further improve currently available models and develop more reliable, flexible, simple and easily accessible tools by incorporating conventional clinicopathological factors as well as molecular biomarkers.

Prostate cell cultures as in vitro models for the study of normal stem cells and cancer stem cells

Current existing therapies for prostate cancer eradicate the majority of cells within a tumor. However, most patients with advanced cancer still progress to androgen-independent metastatic disease that remains essentially incurable by current treatment strategies. Recent evidence has shown that cancer stem cells (CSCs) are a subset of the tumor cells that are responsible for initiating and maintaining the disease. Understanding normal stem cells and CSCs may provide insight into the origin of and new therapeutics for prostate cancer. Normal stem cells and CSCs have been identified in prostate tissue by the use of several markers or techniques. Although research on stem cells has been limited by the lack of suitable in vitro systems, recent studies show that not only primary cells but also several established cell lines may exhibit stem cell properties. This review discusses various in vitro culture systems to propagate normal prostate stem cells and prostate CSCs together with molecular markers. These in vitro cell culture models should be useful for elucidating the differentiation of prostatic epithelium and the biological features of prostate cancer.

Increased Akt and phosphorylated Akt expression are associated with malignant biological features of prostate cancer in Japanese men

To investigate the relationship between the expression of Akt (a serine/threonine kinase that plays a central role in tumorigenesis), phosphorylated Akt (p-Akt), prostate cancer tumour grade, androgen receptor (AR)-staining score, and Ki67 labelling index (LI) in Japanese men. The expression and activation of the cell survival protein Akt was analysed by immunohistochemical staining of paraffin-embedded tissue microarray sections of prostate carcinoma taken from 52 Japanese men who under radical prostatectomy. The correlation between the expression of Akt and p-Akt, and their relationship to primary Gleason grade, AR expression and Ki-67 LI was investigated. The expression of Akt and p-Akt were positively related to primary Gleason grade (Fisher's exact test, P = 0.002 and P = 0.032, respectively). Both AR-staining score and Ki67 LI were were positively related to the expression of Akt (both P < 0.001) and p-Akt (P < 0.001 and P = 0.008, respectively). There was a significant positive correlation between the expression of Akt and p-Akt (Spearman's correlation, r = 0.644, P < 0.001). Increased expression of both Akt and p-Akt were associated with higher tumour grade as well as a higher AR-staining score and Ki67 LI. These data indicate that Akt and p-Akt might be molecular markers for detecting malignant biological features of prostate cancer in the Japanese population.

A comparison of the biological features between prostate cancers arising in the transition and peripheral zones

To investigate differences in the biological features of prostate cancer according to the zonal origin. Among 172 consecutive patients who had a radical prostatectomy (RP), the study included 124 diagnosed as having either transition zone (TZ) or peripheral zone (PZ) cancer, defined according to whether there was > 70% of the cancer area in the TZ or PZ, respectively. The clinicopathological features were then compared between these groups. In addition, the RP specimens were stained immunohistochemically with antibodies to Ki-67, Bcl-2, matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF). Twenty-four patients were diagnosed as having TZ cancer and the remaining 100 as having PZ cancer. Prostate specific antigen (PSA) values in patients with TZ cancer were significantly higher than in those with PZ cancer. Tumour volume in TZ cancer was significantly greater than that in PZ cancer, but there was no significant difference in biochemical recurrence-free survival between the groups. Immunohistochemistry showed that despite there being no differences in Bcl-2 and VEGF expression between TZ and PZ cancers, there was significantly greater expression of Ki-67, MMP-2 and MMP-9 in PZ than TZ cancers. Despite there being no significant difference in biochemical recurrence-free survival after RP between patients with TZ and PZ cancers, there was less cell proliferation and biomarker levels related to invasive potential in TZ than in PZ cancers.