Parameters In Prostate Cancer Research Articles

The effect of puboperiurethral suspension stitch placement on climacturia after robot-assisted laparoscopic radical prostatectomy.

Climacturia is defined as urine leakage associated with orgasm and can negatively affect patients' quality of life. The high prevalence of climacturia after radical prostatectomy (RP) has led to continued efforts to reduce climacturia rates. It has been shown that puboperiurethral suspension stitch placement during RP assists in the recovery of urinary continence. To evaluate the impact of puboperiurethral suspension stitch placement during RP on post-RP climacturia. We conducted a retrospective study of patients who underwent nerve-sparing robot-assisted laparoscopic RP (RALP) at our institution between 2016 and 2023. The patients were categorized into 2 groups: Group 1 (n = 32) that underwent nerve-sparing RALP with puboperiurethral suspension stitch placement and Group 2 (n = 62) that underwent nerve-sparing RALP alone. Patients who were not able to achieve penetration at the last follow-up visit were excluded from the study. The clinical history, parameters of prostate cancer, details of medical and surgical treatments, and follow-up data were evaluated. Differences in sexual and urinary function, climacturia rates, and complications between nerve-sparing RP with and without puboperiurethral suspension stitch placement. There were no significant differences between the groups in terms of surgical complications. The mean follow-up time was 14.62 ± 3.55months in Group 1 and 14.43 ± 4.44months in Group 2 (P = .42). Postoperative erectile functions were similar between the groups. At the last follow-up visit, climacturia was present in 4 patients (12.5%) in Group 1 and 24 patients (38.7%) in Group 2 (P = .016). The long-term stress urinary incontinence rates were similar between the groups. This study provides comparative results on postoperative climacturia rates between nerve-sparing RALP groups with and without puboperiurethral suspension stitch placement. These results show that puboperiurethral suspension stitch can help to prevent postoperative climacturia after RP. This is the first study in the literature that evaluates the effect of puboperiurethral suspension stitch on climacturia. The limitations include the single-center, retrospective design with potential selection bias, possible inaccuracies in the recorded medical data, and challenges in controlling confounding variables. Our study demonstrated that puboperiurethral suspension stitch was a feasible option for the prevention of climacturia after RALP without an increased risk of complications.

The Role of SCARA5 as a Potential Biomarker in Squamous Cell Carcinoma of the Lung.

Lung cancer is the leading cause of cancer-related deaths in the western world. Squamous cell carcinoma is one of the most common histological subtypes of this malignancy. For squamous cell carcinoma of the lung (LSCC), prognostic and predictive markers still are largely missing. In a previous study, we were able to show that the expression of THSD7A shows an association with unfavorable prognostic parameters in prostate cancer. There is also a link to a high expression of FAK. There is incidence that SCARA5 might be the downstream gene of THSD7A. Furthermore, there is evidence that SCARA5 interacts with FAK. We were interested in the role of SCARA5 as a potential biomarker in LSCC. Furthermore, we wanted to know whether SCARA5 expression is linked to THSD7A positivity and to the expression level of FAK. For this reason, we analyzed 101 LSCC tumors by immunohistochemistry. Tissue microarrays were utilized. No significant association was found between SCARA5 expression and overall survival or clinicopathological parameters. There was also no significant association between THSD7A positivity and SCARA5 expression level. Moreover, no significant association was found between FAK expression level and SCARA5 expression level. SCARA5 seems not to play a major role as a biomarker in squamous cell carcinoma of the lung.

The clinical meaning of lymphovascular invasion: preoperative predictors and postoperative implications in prostate cancer - a retrospective study.

Lymphovascular invasion (LVI) is a pivotal histopathological parameter in prostate cancer (PCa), holding significant prognostic implications. Our study pursued a dual objective: firstly, to identify preoperative factors associated with LVI, aiming to unveil markers facilitating the recognition of patients prone to LVI during postoperative examination; and secondly, to assess postoperative outcomes correlated with LVI. We retrospectively analyzed 861 nonmetastatic PCa patients who underwent radical prostatectomy (RP), investigating preoperative factors and postoperative outcomes. Surgical specimens were processed following established guidelines. Statistical analyses utilized non-parametric tests to assess the association between LVI and both pre- and postoperative factors. Furthermore, logistic regression analyses were utilized to develop models aimed at identifying the most significant predictors of LVI and pN1 status, respectively. Numerous preoperative factors exhibited significant correlations with LVI, offering valuable clinical insights. Logistic regression identified magnetic resonance imaging (MRI)-based clinical tumor stage (cT) 3-4, biopsy Gleason Grading Group (GGG) 3-5, preoperative prostate specific antigen (PSA) ≥20 and percentage of positive biopsy cores (PPBC) ≥50% as the strongest preoperative predictors of LVI. Additionally, the study uncovered an association between LVI and postoperative outcomes, including postoperative PSA (p value <0.001), extracapsular extension (ECE) (<0.001), positive surgical margins (PSM) (<0.001), perineural invasion (PNI) (<0.001), pathological tumor stage (pT) (<0.001), pathological lymph node status (pN) (<0.001), postoperative GGG (<0.001), and operative time (0.023). Notably, the study revealed a novel and substantial association between LVI and an increased number of positive lymph nodes in pN+ patients in the univariate analysis (<0.001). Furthermore, we have found an association between LVI and pN1 status in the logistic regression analysis (odds ratio [OR] = 23.905; p <0.001). Our findings underscore the pivotal role of LVI in influencing the prognosis of prostate cancer (PCa). The study acknowledges the challenges associated with preoperative LVI assessment and emphasizes the need for future research to unravel the factors associated with this histopathological finding. Significantly, our research stands out as the first, to the best of our knowledge, toreveal the association between LVI and the number of positive lymph nodes in pN+ patients.

ACOX2 Serves as a Favorable Indicator Related to Lipid Metabolism and Oxidative Stress for Biochemical Recurrence in Prostate Cancer.

Given the heterogeneity of tumors, there is an urgent need for accurate prognostic parameters in prostate cancer (PCa) patients. Lipid metabolism (LM) reprogramming and oxidative stress (OS) play a vital role in the progression of PCa. In this work, we identified five LM-OS-related genes (including ACOX2, PPRAGC1A, PTGS1, PTGS2, and HAO1) associated with the biochemical recurrence (BCR) of PCa. Subsequently, a prognostic signature was established based on these five genes. Kaplan-Meier survival estimates, receiver operating characteristic curves, and relationship analysis between risk score and clinical characters were applied to measure the robustness of the signature in an external cohort. A nomogram of risk score combined with clinical characteristics was constructed for clinical application. Functional enrichment analysis suggested that the underlying mechanism related to the signature included the calcium signaling, lipid transport, and cell cycle signaling pathways. Furthermore, WEE1 inhibitor was identified as a potential agent related to the cell cycle for high-risk patients. The mRNA expression and the prognostic value of the five genes were determined, and ACOX2 was identified as the key gene related to the prognostic signature. The protein expression of ACOX2 was measured in a prostate tissue microarray through an immunohistochemistry assay, confirming the bioinformatics results. By constructing the ACOX2-overexpressing PCa cell lines PC-3 and 22Rv1, the biological function of PCa cells was investigated. The cell viability, colony formation, migration, and invasion ability of PCa cell lines overexpressing ACOX2 were hindered. Decreased cellular lipid content and elevated cellular ROS content were observed in ACOX2-overexpressing PCa cell lines with reduced G2/M phases. In conclusion, this work presents the first prognostic signature specifically focused on LM-OS for PCa. ACOX2 could serve as a favorable indicator for the BCR in PCa. Further experiments are required to identify the potential underlying mechanism.

The Negative Impact of Inflammation-Related Parameters in Prostate Cancer after Robot-Assisted Radical Prostatectomy: A Retrospective Multicenter Cohort Study in Japan (the MSUG94 Group).

Background and Objectives: We aimed to examine the relationship between the inflammation-related parameters, such as the neutrophil-to-lymphocyte ratio (NLR), and the pathological findings and biochemical recurrence (BCR) in patients with prostate cancer (PCa) undergoing robot-assisted radical prostatectomy (RARP). Materials and Methods: A retrospective multicenter cohort study of patients with PCa who underwent RARP at 10 institutes in Japan was conducted. This study enrolled 3195 patients. We focused on patients undergoing RARP who underwent the preoperative measurement of their inflammation-related parameters and who did not receive any neo- or adjuvant therapy. Data on the pre- and postoperative variables for the enrolled patients were obtained. The primary endpoint of this study was the association between BCR and the inflammation-related parameters after RARP. The secondary endpoint was the association between the inflammation-related parameters and the pathological diagnosis of PCa. Results: Data from 2429 patients with PCa who met the study's eligibility criteria were analyzed. The median follow-up period was 25.1 months. The inflammation-related parameters were divided into two groups, and cutoff values were determined based on the receiver operating characteristics. There were no statistically significant differences in biochemical recurrence-free survival for any of the parameters. In the univariate analysis, the NLR was predictive of pathological T3 and lymphovascular invasion; however, there were no significant differences in the multivariate analysis. Conclusions: The inflammation-related parameters did not significantly affect the incidence of BCR, at least among patients with PCa who underwent RARP.

SCARA5 Is Overexpressed in Prostate Cancer and Linked to Poor Prognosis.

Prostate cancer is one of the most common malignancies worldwide, showing a wide range of clinical behaviors. Therefore, several treatment options arise out of the diagnosis "prostate cancer". For this reason, it is desirable to find novel prognostic and predictive markers. In former studies, we showed that THSD7A expression is associated with unfavorable prognostic parameters in prostate cancer and is linked to a high expression of focal adhesion kinase (FAK). Recently, scavenger receptor class A member 5 (SCARA5) was reported to be the downstream gene of THSD7A in esophageal squamous cell carcinoma. SCARA5 is believed to play an important role in the development and progression of several different tumor types. Most studies describe SCARA5 as a tumor suppressor. There is also evidence that SCARA 5 interacts with FAK. To examine the role of SCARA5 as a potential biomarker in prostate cancer, a total of 461 prostate cancers were analyzed via immunohistochemistry using tissue microarrays. Furthermore, we compared the expression level of SCARA5 with our previously collected data on THSD7A and FAK. High SCARA5 expression was associated with advanced tumor stage (p < 0.001), positive nodal status (p < 0.001) and high Gleason-score (p < 0.001). At least, strongly SCARA5-positive cancers were associated with THSD7A-positivity. There was no significant association between SCARA5 expression level and FAK expression level. To our knowledge, we are the first to investigate the role of SCARA5 in prostate cancer and we demonstrated that SCARA5 might be a potential biomarker in prostate cancer.

Automated Ki-67 labeling index assessment in prostate cancer using artificial intelligence and multiplex fluorescence immunohistochemistry.

The Ki-67 labeling index (Ki-67 LI) is a strong prognostic marker in prostate cancer, although its analysis requires cumbersome manual quantification of Ki-67 immunostaining in 200-500 tumor cells. To enable automated Ki-67 LI assessment in routine clinical practice, a framework for automated Ki-67 LI quantification, which comprises three different artificial intelligence analysis steps and an algorithm for cell-distance analysis of multiplex fluorescence immunohistochemistry (mfIHC) staining, was developed and validated in a cohort of 12,475 prostate cancers. The prognostic impact of the Ki-67 LI was tested on a tissue microarray (TMA) containing one 0.6mmsample per patient. A 'heterogeneity TMA' containing three to six samples from different tumor areas in each patient was used to model Ki-67 analysis of multiple different biopsies, and 30 prostate biopsies were analyzed to compare a 'classical' bright field-based Ki-67 analysis with the mfIHC-based framework. The Ki-67 LI provided strong and independent prognostic information in 11,845 analyzed prostate cancers (p< 0.001 each), and excellent agreement was found between the framework for automated Ki-67 LI assessment and the manual quantification in prostate biopsies from routine clinical practice (intraclass correlation coefficient: 0.94 [95% confidence interval: 0.87-0.97]). The analysis of the heterogeneity TMA revealed that the Ki-67 LI of the sample with the highest Gleason score (area under the curve [AUC]: 0.68) was as prognostic as the mean Ki-67 LI of all six foci (AUC: 0.71 [p= 0.24]). The combined analysis of the Ki-67 LI and Gleason score obtained on identical tissue spots showed that the Ki-67 LI added significant additional prognostic information in case of classical International Society of Urological Pathology grades (AUC: 0.82 [p= 0.002]) and quantitative Gleason score (AUC: 0.83 [p= 0.018]). The Ki-67 LI is a powerful prognostic parameter in prostate cancer that is now applicable in routine clinical practice. In the case of multiple cancer-positive biopsies, the sole automated analysis of the worst biopsy was sufficient. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

THSD7A Positivity Is Associated with High Expression of FAK in Prostate Cancer.

Prostate cancer is one of the most common malignancies, and there are a wide range of treatment options after diagnosis. Most prostate cancers behave in an indolent manner. However, a given sub-group has been shown to exhibit aggressive behavior; therefore, it is desirable to find novel prognostic and predictive (molecular) markers. THSD7A expression is significantly associated with unfavorable prognostic parameters in prostate cancer. FAK is overexpressed in several tumor types and is believed to play a role in tumor progression and metastasis. Furthermore, there is evidence that THSD7A might affect FAK-dependent signaling pathways. To examine whether THSD7A expression has an impact on the expression level of FAK in its unphosphorylated form, a total of 461 prostate cancers were analyzed by immunohistochemistry using tissue microarrays. THSD7A positivity and low FAK expression were associated with adverse pathological features. THSD7A positivity was significantly associated with high FAK expression. To our knowledge we are the first to show that THSD7A positivity is associated with high FAK expression in prostate cancer. This might be proof of the actual involvement of THSD7A in FAK-dependent signaling pathways. This is of special importance because THSD7A might also serve as a putative therapeutic target in cancer therapy.

The prognostic value of mean apparent diffusion coefficient measured with diffusion-weighted magnetic resonance image in patients with prostate cancer treated with definitive radiotherapy

PurposeTo assess the correlation between initial tumor apparent diffusion coefficient (ADC) values and clinicopathological parameters in prostate cancer (PCa) patients treated with definitive radiotherapy (RT). Additionally, the prognostic factors for freedom from biochemical failure (FFBF) and progression-free survival (PFS) in this patient cohort were analyzed. Materials and methodsThe clinical data of 503 patients with biopsy-confirmed PCa were evaluated retrospectively. All patients had clearly evident tumors on diffusion-weighted magnetic resonance imaging (DW-MRI) for ADC values. Univariable and multivariable analyses were used to determine prognostic factors for FFBF and PFS. ResultsThe median follow-up was 72.9 months. The 5-year FFBF and PFS rates were 93.2% and 86.2%, respectively. Significantly lower ADC values were found in patients with a high PSA level; advanced clinical stage; higher ISUP score, and higher risk group than their counterparts. Receiver operating characteristic (ROC) curve analysis revealed an ADC cut-off value of 0.737 × 10−3 mm2/sec for tumor recurrence. Patients who progressed had a lower mean ADC value than those who did not (0.712 ± 0.158 vs. 1.365 ± 0.227 × 10−3 mm2/sec; p < 0.001). There was a significant difference in 5-year FFBF (96.3% vs. 90%; p < 0.001) and PFSrates (83.8% vs. 73.5%; p = 0.002) between patients with higher and lower mean ADC values. The FFBF and PFS were found to be correlated with tumor ADC value and ISUP grades in multivariable analysis. Additionally, older age was found to be a significant predictor of worse PFS. ConclusionsLower ADC values were found in patients with high-risk characteristics such as a high serum PSA level, stage or grade of tumor, or high-risk disease, implying that ADC values could be used to predict prognosis. Lower ADC values and higher ISUP grades were associated with an increased risk of BF and progression, implying that treatment intensification may be required in these patients.

Analysis of Apparent Diffusion Coefficient Value and Dynamic Contrast-Enhanced Magnetic Resonance Imaging Parameters of Prostate Cancer Patients after Diagnosis and Treatment with Magnetic Resonance Imaging.

This research was aimed at exploring the changes in the apparent diffusion coefficient (ADC) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters of prostate cancer (PCa) patients. Sixty PCa patients from the hospital were recruited as the research object, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) scans were performed to determine the shape, scope, and enhancement characteristics of prostate lesions and their relationship with surrounding tissues. The quantitative parameters of ADC and DCE-MRI were measured. There were 4 patients (6.67%) with a Gleason score of 6 and 15 patients (25%) with a 4 + 3 score. The ADC with Gleason = 6 is 0.81 ± 0.08 × 10−3 s/mm2, the ADC with Gleason = 3 + 4 is 0.74 ± 0.07 × 10−3 s/mm2, the ADC with Gleason = 4 + 3 is 0.73 ± 0.05 × 10−3 s/mm2, the ADC with Gleason = 9 is 0.65 ± 0.06 × 10−3 s/mm2, and the ADC with Gleason = 10 is 0.59 ± 0.07 × 10−3 s/mm2. As the Gleason score increased, the ADC decreased and the permeation parameter transfer constant increased. When the ADC was combined with the permeability parameter transfer constant, the AUC of Gleason = 6 points and Gleason = 7 points was greatly different (P < 0.05). The 95% CI of the ADC combined permeability parameter transport constant when Gleason = 6 points and Gleason = 7 points was 0.898-0.934, the sensitivity was 75.4%, and the specificity was 86.2%. The ADC value was negatively correlated with Gleason score. The ADC value combined with VTC value has good diagnostic performance in evaluating the invasion of PCa, which is very important for making treatment plan and evaluating prognosis.

Abstract 483: Automated Ki67-LI assessment in prostate cancer using artificial intelligence in multiplex fluorescence immunohistochemistry

Abstract The Ki67 labeling index (Ki67-LI) is a strong prognostic marker in prostate cancer. Its analysis requires cumbersome manual quantification of Ki67 immunostaining in at least 200 tumor cells. To enable automated Ki67-LI assessment in routine clinical practice, we have developed and validated a framework for automated Ki67-LI quantification, which comprises three different artificial intelligence analysis steps and an algorithm for cell-distance analysis of multiplex fluorescence immunohistochemistry staining. The prognostic impact of the Ki67-LI was tested on a tissue microarray (TMA) containing one sample each of 12475 prostate cancers. A “heterogeneity TMA” containing 3 to 6 samples from different tumor areas was used to model Ki67 analysis of multiple different biopsies. The Ki67-LI provided strong and independent prognostic information in 11845 successfully analyzed prostate cancers (p&amp;lt;0.001 each). The analysis of the heterogeneity TMA revealed that the Ki67-LI of the sample with the highest Gleason score (AUC:0.68) was similarly prognostic as the mean Ki67-LI of all six foci (AUC:0.71 [p=0.24]). The combined analysis of the Ki67-LI and Gleason grades obtained on identical tissue spots showed that the Ki67-LI added significant additional prognostic information in case of classical ISUP grades (AUC:0.82 [p=0.002]) and quantitative Gleason grades (AUC:0.83 [p=0.018]). The Ki67-LI is a powerful prognostic parameter in prostate cancer, which can be efficiently analyzed in multiplex fluorescence IHC. In case of multiple cancer positive biopsies, the sole analysis of the worst biopsy can be sufficient. Citation Format: Niclas C. Blessin, Tim Mandelkow, Elena Bady, Ronald Simon, Claudia Hube-Magg, Maximilian Lennartz, Guido Sauter, Markus Graefen, Stefan Steurer. Automated Ki67-LI assessment in prostate cancer using artificial intelligence in multiplex fluorescence immunohistochemistry [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 483.

HRM method for identification of TP53 exon 5 and 8 mutations in human prostate cancer patients

BackgroundThe purpose of the present study was to perform a high-resolution melting (HRM) analysis to discover mutations in gene exons 5–8 of tumor protein p53 (TP53), as well as the relationships of these mutations to clinical parameters in prostate cancer (PC). MethodsGenomic DNA was extracted from 50 formalin-fixed paraffin-embedded (FFPE) tissues with PC. Mutations in exons 5 and 8 of TP53 were analyzed using the HRM method. Sanger sequencing was used to describe mutations. ResultsAccording to the HRM analysis results, 21 (42%) PC samples had different normalized and shifted melting curves from other samples. Mutations in TP53 exons 5 and8 were observed in 12 (24%) patients by the Sanger method. The detection sensitivity of the HRM method in exon 5 and exon 8 mutations was 66.7% and 50%, respectively. PSA levels of PC patients with TP53 mutation were found to be lower than that of patients with no mutation (p = 0.8270). However, we did not find any correlations between TP53 mutations and clinical parameters (p > 0.05). ConclusionsHRM analysis is a simple, rapid, and efficient mutation-scanning method for known/unknown mutations in TP53 exons 5and8, as well as an attractive method for detection of mutations and their analysis in FFPE tissues. Additional studies with larger patient populations are warranted to confirm the correlation between the TP53 mutations and PC risk.

Contemporary Grading of Prostate Cancer: The Impact of Grading Criteria and the Significance of the Amount of Intraductal Carcinoma.

Simple SummaryPrognostic grade group is an important prognostic parameter in prostate cancer, guiding therapeutic decisions. The cribriform pattern and intraductal carcinoma are histologic patterns with additional prognostic significance and their presence should be commented upon in pathology reports. The cribriform pattern is included in grade grouping. Controversies exist regarding the grading of intraductal carcinoma. The grading of tertiary patterns is another point of disagreement in the recently published guidelines. In this study, we sought to address the impact of the different guidelines in prostate cancer grading of prostatectomy specimens. The association of the amount of intraductal carcinoma to pathologic parameters was also analyzed. Our study highlights the potential of confusion among pathologists and clinicians in regard to prostate cancer grading and underscores the need for a consensus grading system.(1) Background: Prognostic grade group (PGG) is an important prognostic parameter in prostate cancer that guides therapeutic decisions. The cribriform pattern and intraductal carcinoma (IDC) are two histological patterns, that have additional prognostic significance. However, discrepancies exist regarding the handling of IDC according to the guidelines published by two international genitourinary pathology societies. Furthermore, whether, in addition to its presence, the amount of IDC is also of importance has not been studied before. Lastly, the handling of tertiary patterns has also been a matter of debate in the literature. (2) Methods: A total of 129 prostatectomy cases were retrieved and a detailed histopathologic analysis was performed. (3) Results: Two cases (1.6%) upgraded their PGG, when IDC was incorporated in the grading system. The presence and the amount of IDC, as well as the presence of cribriform carcinoma were associated with adverse pathologic characteristics. Interestingly, in six cases (4.7%) there was a difference in PGG when using the different guidelines regarding the handling of tertiary patterns. In total, 6.2% of the cases would be assigned a different grade depending on the guidelines followed. (4) Conclusions: These findings highlight a potential area of confusion among pathologists and clinicians and underscore the need for a consensus grading system.

Clinicopathological Analysis of the ISUP Grade Group And Other Parameters in Prostate Cancer: Elucidation of Mutual Impact of the Various Parameters.

BackgroundProstate cancer has become increasingly common worldwide. Although Grade group (GG) is widely accepted as an indicator of prostate cancer grade, there are malignancies that cannot be defined by GG alone. Moreover, the relationship between GG and other parameters remains unclear. Herein, we aimed to explore the biological characteristics of prostate cancer.MethodsThis study included 299 radical prostatectomy cases. The Chi-square test and analysis of variance were used to analyze the association of GG with binary and continuous variables. We then conducted morphological analyses. Multivariate analyses were performed to extract the data on risk factors for biochemical recurrence (BCR) and lymph node metastasis.ResultsThe lymphatic, venous, perineural, and seminal vesicle invasion rates were 37/299 (12.4%), 25/299 (8.4%), 280/299 (93.6%), and 23/299 (7.7%), respectively. The extraprostatic extension (EPE), positive surgical margin, tertiary Gleason pattern 5, intraductal carcinoma of the prostate gland, and lymph node metastasis rates were 89/299 (29.8%), 106/299 (35.5%), 33/260 (12.7%), 56/299 (18.7%), and 23/299 (7.7%), respectively. As GG increased, various parameters became easier to visualize; however, there were differences between the parameters. Postoperative BCR was observed in 31/242 (12.8%) cases without preoperative hormone therapy; GG2, GG3, GG4, and GG5 accounted for 4, 7, 7, and 13 cases, respectively. Multivariate analyses revealed that GG and tumor diameter were significant risk factors for early BCR, whereas lymphatic invasion, EPE, and seminal vesicle invasion were significant risk factors for lymph node metastasis. For BCR, the odds ratios (ORs) for GG and tumor diameter were 2.253 (95% confidence interval (CI]): 1.297–3.912; P=0.004) and 1.074 (95% CI: 1.011–1.142; P=0.022), respectively. For lymph node metastasis, ORs for the presence of lymphatic invasion, EPE, and seminal vesicle invasion were 7.425 (95% CI: 1.688–22.583; P=0.004), 4.391 (95% CI: 1.037–18.589; P=0.044), and 5.755 (95% CI: 1.308–25.316; P=0.021), respectively.ConclusionsWe summarized various parameters correlating with each GG. Through multivariate analyses, we established the independent risk factors for early BCR and lymph node metastasis. In addition to GG, other important indices of malignancy were determined and weighted to provide a basis for future investigations.

Expression of cysteine-rich protein 61 protein in prostate carcinoma and their clinical significance

Objective To investigate the expression and clinical significance of Cysteine-rich protein 61 (Cyr61) protein in prostate cancer. Methods We selected 68 cases of the prostate cancer tissues and 60 cases of benign prostatic hyperplasia tissues in our hospital. Immunohistochemistry was used to detect the expression of Cyr61 protein in prostate cancer tissues and benign prostatic hyperplasia tissues, and then the difference of expression between the two groups and its relationship with pathological parameters of prostate cancer were analyzed. Results The expression of Cyr61 protein in prostate cancer tissues was significantly higher than that in benign prostatic hyperplasia tissues (85.3% vs. 8.3%, χ2=75.536, P 0.05), TNM staging (χ2=0.342, P>0.05), regional lymph node metastasis (χ2=0.176, P>0.05) and distant metastasis (χ2=0.673, P>0.05), but was significantly correlated with preoperative total prostate specific antigen (tPSA) level (χ2=8.492, P<0.05), differentiation degree (χ2=13.028, P<0.05) and Gleason scores (χ2=4.032, P<0.05). Conclusion The expression of Cyr61 protein in prostate cancer tissues were significantly up-regulated, which helps to assess the progress of prostate cancer. Key words: Cysteine-rich protein 61 protein; Prostate carcinoma; Expression

Dynamic contrast-enhanced (DCE) MR imaging: the role of qualitative and quantitative parameters for evaluating prostate tumors stratified by Gleason score and PI-RADS v2.

To investigate the role of qualitative and quantitative DCE-MRI parameters in prostate cancer (PCa) stratified by whole-mount histopathology (WMHP) Gleason score (GS) and PI-RADSv2. This retrospective study included 323 PCa tumors in 254 men, who underwent 3T MRI prior to prostatectomy, 7/2009-12/2016. Qualitative DCE curve types included type 1 (progressive), type 2 (plateau) and type 3 (washout). Quantitative DCE-MRI pharmacokinetic (PK) parameters included Ktrans (influx volume transfer coefficient), Kep (efflux reflux rate constant) and iAUC (initial area under the curve). DCE-MRI features of true positive lesions were evaluated for overall, index, transition zone (TZ) and peripheral zone (PZ), based on GS grade (low = 6, high > 6) and PI-RADSv2 score using SPSSv24. There were 57 (17.6%) low-grade and 266 (82.4%) high-grade PCa lesions. PI-RADSv2 3, 4 and 5 included 106, 120 and 97 lesions, respectively. 251 (77.7%) and 72 (22.3%) lesions were located in PZ and TZ, respectively. High-grade lesions had significantly higher proportion of Type 3 curves compared to low-grade lesions in overall (70.3% vs. 54.4%) and TZ (73.5% vs. 43.5%). As PI-RADSv2 increased, the proportion of type 3 curve significantly increased for overall (80.4-51.9%), index (80.4-54.7%) and PZ (78.7-52.1%) lesions. Among PK parameters, Ktrans (0.43 vs 0.32) and iAUC (8.99 vs 6.9) for overall PCa, Ktrans (0.43 vs 0.31) and iAUC (9 vs 6.67) for PZ PCa, and iAUC (8.94 vs 7.42) for index PCa were significantly higher for high-grade versus low-grade lesions. Also, Ktrans (0.51-0.34), Kep (1.75-1.29) and iAUC (9.79-7.6) for overall PCa, Ktrans (0.53-0.32), Kep (1.81-1.26) and iAUC (9.83-7.34) for PZ PCa; and Kep (1.79-1.17) and iAUC (11.3-8.45) for index PCa increased significantly with a higher PI-RADSv2 score. The results of study show the possible utility of qualitative and quantitative DCE-MRI parameters for assessment of PCa GS and PI-RADSv2 categorization.

Prognostic and diagnostic role of PSA immunohistochemistry: A tissue microarray study on 21,000 normal and cancerous tissues

To assess the prognostic and diagnostic utility of PSA immunostaining, tissue microarrays containing 17,747 prostate cancers, 3,442 other tumors from 82 different (sub) types and 608 normal tissues were analyzed at two different antibody concentrations (1:100 and 1:800). In normal tissues, PSA expression was limited to prostate epithelial cells. In prostate cancers, PSA staining was seen in 99.9–100% (1:800–1:100) primary tumors, 98.7–99.7% of advanced recurrent cancers, in 84.6–91.4% castration resistant cancers, and in 7.7–18.8% of 16 small cell carcinomas. Among extraprostatic tumors, PSA stained positive in 0–3 (1:800-1:100) of 19 osteosarcomas, 1-2 of 34 ovarian cancers, 0-2 of 35 malignant mesotheliomas, 0–1 of 21 thyroid gland carcinomas and 0–1 of 26 large cell lung cancers. Reduced staining intensity and loss of apical staining were strongly linked to unfavorable tumor phenotype and poor prognosis (p < 0.0001 each). This was all the more the case if a combined “PSA pattern score” was built from staining intensity and pattern. The prognostic impact of the “PSA pattern score” was independent of established pre- and postoperative clinico-pathological prognostic features. In conclusion, PSA immunostaining is a strong prognostic parameter in prostate cancer and has high specificity for prostate cancer at a wide range of antibody dilutions.

Lymphatic micrometastases predict biochemical recurrence in patients undergoing radical prostatectomy and pelvic lymph node dissection for prostate cancer.

Nodal metastasis is a strong prognostic parameter in prostate cancer (PCa). We analysed the detection of micrometastases (miN + ) in initially nodal-negative (pN0) radical prostatectomy specimens from pT2a-c and pT3a PCa patients by immunohistochemistry (IHC). A total of 2352 lymph nodes of 193 PCa patients were centrally re-examined for miN + or miN- status using IHC. Results were correlated with clinical and follow-up data. Recurrence-free survival (RFS) was calculated with the log-rank test using the Kaplan-Meier method. In addition, a logistic regression analysis was performed. IHC detected miN + in a total of 17 patients (8.8 %). miN + seemed to be significantly associated with a higher Gleason score and was detected in more advanced pT stages. A total of 45 patients (23.1 %) had a biochemical recurrence (BCR). BCR was associated with miN +. Patients with miN + had a significantly shorter RFS (22.9 versus 58.7 months; p < 0.001). In the univariate (OR: 5.04; 95 % CI: 2.46 - 10.6; p-value: < 0.0001) and multivariate (OR: 3.29; 95 % CI: 1.54 - 7.08; p-value: 0.002) regression model, the miN + status was the strongest predictor of a BCR. IHC seems to be of high diagnostic value for the detection of micrometastases in initially nodal-negative PCa patients. IHC should therefore be performed in PCa patients with nodal-negative findings.

Improved repeatability of dynamic contrast-enhanced MRI using the complex MRI signal to derive arterial input functions: a test-retest study in prostate cancer patients.

PurposeThe arterial input function (AIF) is a major source of uncertainty in tracer kinetic (TK) analysis of dynamic contrast‐enhanced (DCE)‐MRI data. The aim of this study was to investigate the repeatability of AIFs extracted from the complex signal and of the resulting TK parameters in prostate cancer patients.MethodsTwenty‐two patients with biopsy‐proven prostate cancer underwent a 3T MRI exam twice. DCE‐MRI data were acquired with a 3D spoiled gradient echo sequence. AIFs were extracted from the magnitude of the signal (AIFMAGN), phase (AIFPHASE), and complex signal (AIFCOMPLEX). The Tofts model was applied to extract Ktrans, kep and ve. Repeatability of AIF curve characteristics and TK parameters was assessed with the within‐subject coefficient of variation (wCV).ResultsThe wCV for peak height and full width at half maximum for AIFCOMPLEX (7% and 8%) indicated an improved repeatability compared to AIFMAGN (12% and 12%) and AIFPHASE (12% and 7%). This translated in lower wCV values for Ktrans (11%) with AIFCOMPLEX in comparison to AIFMAGN (24%) and AIFPHASE (15%). For kep, the wCV was 16% with AIFMAGN, 13% with AIFPHASE, and 13% with AIFCOMPLEX.ConclusionRepeatability of AIFPHASE and AIFCOMPLEX is higher than for AIFMAGN, resulting in a better repeatability of TK parameters. Thus, use of either AIFPHASE or AIFCOMPLEX improves the robustness of quantitative analysis of DCE‐MRI in prostate cancer.

Impact of the SPOP Mutant Subtype on the Interpretation of Clinical Parameters in Prostate Cancer.

PurposeMolecular characterization of prostate cancer, including The Cancer Genome Atlas, has revealed distinct subtypes with underlying genomic alterations. One of these core subtypes, SPOP (speckle-type POZ protein) mutant prostate cancer, has previously only been identifiable via DNA sequencing, which has made the impact on prognosis and routinely used risk stratification parameters unclear.MethodsWe have developed a novel gene expression signature, classifier (Subclass Predictor Based on Transcriptional Data), and decision tree to predict the SPOP mutant subclass from RNA gene expression data and classify common prostate cancer molecular subtypes. We then validated and further interrogated the association of prostate cancer molecular subtypes with pathologic and clinical outcomes in retrospective and prospective cohorts of 8,158 patients.ResultsThe subclass predictor based on transcriptional data model showed high sensitivity and specificity in multiple cohorts across both RNA sequencing and microarray gene expression platforms. We predicted approximately 8% to 9% of cases to be SPOP mutant from both retrospective and prospective cohorts. We found that the SPOP mutant subclass was associated with lower frequency of positive margins, extraprostatic extension, and seminal vesicle invasion at prostatectomy; however, SPOP mutant cancers were associated with higher pretreatment serum prostate-specific antigen (PSA). The association between SPOP mutant status and higher PSA level was validated in three independent cohorts. Despite high pretreatment PSA, the SPOP mutant subtype was associated with a favorable prognosis with improved metastasis-free survival, particularly in patients with high-risk preoperative PSA levels.ConclusionUsing a novel gene expression model and a decision tree algorithm to define prostate cancer molecular subclasses, we found that the SPOP mutant subclass is associated with higher preoperative PSA, less adverse pathologic features, and favorable prognosis. These findings suggest a paradigm in which the interpretation of common risk stratification parameters, particularly PSA, may be influenced by the underlying molecular subtype of prostate cancer.