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Urology Journal Dec 2022The aim of this study was to investigate the diagnostic performance of mpMRI for detecting cribriform pattern prostate cancer.
BACKGROUND
The aim of this study was to investigate the diagnostic performance of mpMRI for detecting cribriform pattern prostate cancer.
MATERIALS AND METHODS
This study retrospectively enrolled 33 patients who were reported cribriform pattern prostate cancer at final pathology. The localization, grade and volumetric properties of the dominant tumors and areas with cribriform pattern at the final pathological specimens were recorded and the diagnostic value of mpMRI was evaluated on the basis of the cribriform morphology detection rate. It was analyzed using Wilcoxon test, the Chi-square test and Fisher's Exact test. The significance level (P-value) was set at .05 in all statistical analyses.
RESULTS
A total of 58 prostate cancer foci were (38 cribriform, 20 non-cribriform foci) identified on the final pathology. mpMRI identified 36 of the 38 cribriform morphology harboring tumor foci with a sensitivity of 94.7% (95% confidence interval 82.7-98.5%). In 17 of the 33 patients mpMRI detected single lesion and for these lesions; mpMRI identified cribriform morphology positive areas precisely in 15 patients with significantly low ADCmean and ADCmin values compared to the non-cribriform cancer areas within the primary index lesion (P < .001). For the remaining 16 patients with multiple lesions; all of the tumor foci that harboring cribriform morphology were identified by mpMRI but in none of them any ADCmean and ADCmin value divergence were detected between the cribriform and non-cribriform pattern tumor foci within the primary index lesion.
CONCLUSION
Cribiform pattern should be considered in single lesions with an area of lower ADC value on mpMRI.
Topics: Male; Humans; Multiparametric Magnetic Resonance Imaging; Prostate; Retrospective Studies; Prostatic Neoplasms; Adenocarcinoma; Magnetic Resonance Imaging; Prostatectomy
PubMed: 36528799
DOI: 10.22037/uj.v19i.7382 -
Journal of Cancer Research and... Apr 2023Tumor-associated macrophages (TAM) are the main component of inflammation along with leukocytes, endothelial cells and fibroblasts together form a tumor... (Observational Study)
Observational Study
BACKGROUND
Tumor-associated macrophages (TAM) are the main component of inflammation along with leukocytes, endothelial cells and fibroblasts together form a tumor microenvironment, with immune cells representing its vital component. Many studies suggested that TAMs cumulating in tumors correlate with a poor prognosis. In prostate cancer, TAMs can increase cancer cell invasion by stimulating tumor angiogenesis, degrading the extracellular matrix, and also suppresses the antitumor functions of cytotoxic T cells resulting in poor prognosis.
AIMS AND OBJECTIVES
: 1. To determine the expression of M1 (CD68) and M2 (CD163) in prostate carcinoma (Pca). 2. To find the association between M1, M2 macrophage with Gleason's score and stage of Pca.
MATERIALS AND METHODS
: This is a retrospective observational study. All transurethral resection prostatic (TURP) chips positive for Pca and the clinical details were collected. Radiologic findings with respect to stage of disease, size of lesion, were noted.
RESULTS
Among the 62 cases studied, majority of the cases were in-between the age of 61-70 years. Highest cases were seen in Gleason's score 8, 9, and 10 (62%), prostatic specific antigen (PSA) levels 20-80 ng/mL (64%), tumor size 3-6 cm (51.6%), T3 stage (40.3%), N1 lymph node stage (70.9%). M1 stage of (31%). CD68 and CD163 expression was analyzed with Gleason's score, TNM stage and PSA levels. CD68 score 3 correlated with low distant and nodal metastasis 6.2% and 6.8%, respectively. CD163 score 3 correlated with high metastasis to lymph nodes and distant metastasis of 86.3% and 25%, respectively. On further analysis, statistically convincing association between the CD163 expression and Gleason's score, PSA levels, nodal and distant metastasis was found.
CONCLUSION
CD68 expression was correlated with good prognosis with less nodal and distant metastasis and Cd163 expression has poor outcome with increased chances of nodal and distant metastasis. Further exploration of TAM mechanisms and immune checkpoints in the prostate tumor microenvironment can furnish new light and motives for the treatment of Pca.
Topics: Male; Humans; Middle Aged; Aged; Prostate-Specific Antigen; Tumor-Associated Macrophages; Prostate; Endothelial Cells; Prostatic Neoplasms; Carcinoma; Prognosis; Tumor Microenvironment
PubMed: 37148007
DOI: 10.4103/jcrt.jcrt_497_22 -
Technology in Cancer Research &... 2020Several techniques have been employed for deletion of the NKX3.1 gene, resulting in developmental defects of the prostate, including alterations in ductal branching...
Several techniques have been employed for deletion of the NKX3.1 gene, resulting in developmental defects of the prostate, including alterations in ductal branching morphogenesis and prostatic secretions as well as epithelial hyperplasia and dysplasia. To investigate whether the CRISPR/Cas9-mediated technique can be applied to study prostate carcinogenesis through exon I deletion of NKX3.1 gene, alterations in the prostatic intraepithelial neoplasia (PIN) and their regulatory mechanism were observed in the prostate of NKX3.1 knockout (KO) mice produced by the CRISPR/Cas9-mediated NKX3.1 mutant gene, at the ages of 16 and 24 weeks. The weight of dorsal-lateral prostate (DLP) and anterior prostate (AP) were observed to be increased in only the 24 weeks KO mice, although morphogenesis was constant in all groups. Obvious PIN 1 and 2 lesions were frequently detected in prostate of the 24 weeks KO mice, as compared with the same age wild type (WT) mice. Ki67, a key indicator for PIN, was densely stained in the epithelium of prostate in the 24 weeks KO mice, while the expression of p53 protein was suppressed in the same group. Also, both the 16 and 24 weeks KO mice reveal inhibition of the PI3K/AKT/mTOR pathway in the prostate. However, prostate specific antigen (PSA) levels and Bax/Bcl-2 expressions were decreased in the prostate of 16 weeks KO mice, and were increased in only the 24 weeks KO mice. Taken together, the results of the present study provide additional evidence that CRISPR/Cas9-mediated exon 1 deletion of the NKX3.1 gene successfully induces PIN lesions, along with significant alterations of Ki67 expression, EGFR signaling pathway, and cancer-regulated proteins.
Topics: Animals; CRISPR-Cas Systems; ErbB Receptors; Homeodomain Proteins; Humans; Ki-67 Antigen; Male; Mice; Mice, Knockout; Morphogenesis; Prostate; Prostatic Intraepithelial Neoplasia; Transcription Factors; Tumor Suppressor Protein p53
PubMed: 33094683
DOI: 10.1177/1533033820964425 -
Real-time diagnosis and Gleason grading of prostate core needle biopsies using nonlinear microscopy.Modern Pathology : An Official Journal... Apr 2022Rapid histologic assessment of fresh prostate biopsies may reduce patient anxiety, aid in biopsy sampling, and enable specimen triaging for molecular/genomic analyses...
Rapid histologic assessment of fresh prostate biopsies may reduce patient anxiety, aid in biopsy sampling, and enable specimen triaging for molecular/genomic analyses and research that could benefit from fresh tissue analysis. Nonlinear microscopy (NLM) is a fluorescence microscopy technique that can produce high-resolution images of freshly excised tissue resembling formalin-fixed paraffin-embedded (FFPE) H&E. NLM enables evaluation of tissue up to ~100 µm below the surface, analogous to serial sectioning, but without requiring microtome sectioning. One hundred and seventy biopsies were collected from 63 patients who underwent in-bore MRI or MRI/ultrasound fusion biopsy procedures. Biopsies were stained in acridine orange and sulforhodamine 101, a nuclear and cytoplasmic/stromal fluorescent dye, for 45 s. Genitourinary pathologists evaluated the biopsies using NLM by translating the biopsies in real time to areas of interest and NLM images were recorded. After NLM evaluation, the biopsies were processed for standard FFPE H&E and similarities and differences between NLM and FFPE H&E were investigated. Accuracies of NLM diagnoses and Gleason scores were calculated using FFPE histology as the gold standard. Pathologists achieved a 92.4% sensitivity (85.0-96.9%, 95% confidence intervals) and 100.0% specificity (94.3-100.0%) for detecting carcinoma compared to FFPE histology. The agreement between the Grade Group determined by NLM versus FFPE histology had an unweighted Cohen's Kappa of 0.588. The average NLM evaluation time was 2.10 min per biopsy (3.08 min for the first 20 patients, decreasing to 1.54 min in subsequent patients). Further studies with larger patient populations, larger number of pathologists, and multiple institutions are warranted. NLM is a promising method for future rapid evaluation of prostate needle core biopsies.
Topics: Biopsy; Biopsy, Large-Core Needle; Humans; Male; Microscopy, Fluorescence; Neoplasm Grading; Prostate; Prostatic Neoplasms
PubMed: 34725447
DOI: 10.1038/s41379-021-00960-1 -
Disease Markers 2022To investigate the effect of bicalutamide combined with docetaxel on the levels of prostate-specific antigen (PSA) in serum and vascular endothelial growth factor (VEGF)...
OBJECTIVE
To investigate the effect of bicalutamide combined with docetaxel on the levels of prostate-specific antigen (PSA) in serum and vascular endothelial growth factor (VEGF) in patients with advanced prostate carcinoma (PCa).
METHODS
The clinical data of 103 patients with advanced PCa at our hospital between Feb. 2020 and Feb. 2021 were retrospectively analyzed, the 90 of whom screened by inclusion and exclusion criteria were finally chosen as research objects. They were divided into a control group and an experimental group according to the order of admission, with 45 cases in each group. The control group was treated with conventional treatment, while the experimental group underwent the combination of bicalutamide and docetaxel, and the clinical indices of the two groups were compared.
RESULTS
After treatment, the serum indices in the experimental group were remarkably lower than those in the control group ( < 0.001), with remarkably lower incidence of toxic and side effects ( < 0.05) and higher Expanded Prostate Cancer Index Composite (EPIC) scores ( < 0.001) in the experimental group than in the control group.
CONCLUSION
The implementation of bicalutamide combined with docetaxel in patients with advanced PCa is effective in reducing the inflammatory expression and improving quality of life and has a higher safety profile. Compared with conventional treatment, this method is of high application value, and further studies will help establish a better solution for such patients.
Topics: Anilides; Carcinoma; Docetaxel; Humans; Male; Nitriles; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Quality of Life; Retrospective Studies; Tosyl Compounds; Vascular Endothelial Growth Factor A
PubMed: 36033830
DOI: 10.1155/2022/4506350 -
International Journal of Surgical... Sep 2023Lymphovascular invasion (LVI) is an adverse pathological finding in radical prostatectomy (RP) specimens associated with increased risk of metastatic disease. Its...
Lymphovascular invasion (LVI) is an adverse pathological finding in radical prostatectomy (RP) specimens associated with increased risk of metastatic disease. Its variable incidence may be attributed to underreporting. We characterized the location, quantity, and morphology of LVI foci in RP specimens and assessed the relationship between LVI and cribriform and intraductal carcinoma and metastatic risk. . Two pathologists reviewed retrospectively 54 RP specimens reported as positive for LVI. Ambiguous cases were confirmed by immunostaining for ERG, CD31 and D2-40. . In 4/54 (7.4%), LVI could not be confirmed. Main mimickers of LVI were retraction artifact and dislodged tumor cells. Based on our review, the most important criteria to distinguish LVI from its mimickers were a corrugated lining of vascular spaces, endothelial nuclei bulging into the lumen, and presence of proteinaceous material. The LVI frequency per case ranged from 1 to 109 (median 7.5). In 47/50 (94%) cases with LVI, the associated carcinoma comprised cribriform pattern and/or intraductal carcinoma. The most common morphology of LVI foci was cribriform, occurring in 43/50 specimens, representing 469/843 (56%) of LVI foci. Most LVI foci were intraprostatic and located at the carcinoma-stroma interface. Particularly the risk of bone metastases during follow-up was independently associated with higher frequency of LVI foci ( = .009). . The detailed description of prostatic LVI, and awareness of their predominant location and morphology may help its identification and improve the diagnostic accuracy of LVI in pathology reporting. The clinical impact of LVI quantification in prostate cancer needs validation by further studies.
Topics: Humans; Male; Carcinoma, Intraductal, Noninfiltrating; Neoplasm Invasiveness; Prognosis; Prostate; Prostatectomy; Prostatic Neoplasms; Retrospective Studies
PubMed: 35816346
DOI: 10.1177/10668969221110456 -
Archives of Pathology & Laboratory... Jan 2023Intraductal carcinoma of the prostate (IDC-P) is considered a distinct form of aggressive prostate cancer where comedonecrosis, a grade 5 pattern, is occasionally...
CONTEXT.—
Intraductal carcinoma of the prostate (IDC-P) is considered a distinct form of aggressive prostate cancer where comedonecrosis, a grade 5 pattern, is occasionally present. Meanwhile, assigning a Gleason grade to IDC-P remains controversial.
OBJECTIVE.—
To assess the clinical significance of necrosis associated with IDC-P.
DESIGN.—
We compared radical prostatectomy (RP) findings and oncologic outcomes in men with prostate cancer exhibiting IDC-P with (IDC-P+/N+) versus without (IDC-P+/N-) comedonecrosis.
RESULTS.—
Of the 558 RPs examined, IDC-P was present in 213 cases (38.2%), including 167 (78.4%) with IDC-P+/N- and 46 (21.6%) with IDC-P+/N+. When comparing IDC-P+/N- versus IDC-P+/N+ cases, the presence of necrosis was significantly associated with higher tumor grade, higher incidence of pT3/pT3b or pN1 disease, and larger estimated tumor volume. Outcome analysis revealed a significantly higher risk of disease progression in IDC-P+/N+ patients than in IDC-P+/N- patients (P < .001). Significant differences in progression-free survival between IDC-P+/N- and IDC-P+/N+ patients were also seen in subgroups, such as those without (P = .01) or with (P = .03) adjuvant therapy immediately after RP, those with pN0 disease (P < .001), and, more interestingly, those exhibiting conventional Gleason pattern 5 component (P = .02). Multivariate analysis showed significance for IDC-P+/N+ when IDC-P (grade 4) and IDC-P+/N+ (grade 5) were (hazard ratio, 1.768; P = .049) or were not (hazard ratio, 2.000; P = .008) incorporated into the Gleason score.
CONCLUSIONS.—
IDC-P+/N+ was found to be associated with worse histopathologic features on RP and poorer prognosis as an independent predictor. Pathologists may thus need to report the presence or absence of not only IDC-P but also comedonecrosis within IDC-P.
Topics: Male; Humans; Prostate; Carcinoma, Intraductal, Noninfiltrating; Prostatic Neoplasms; Neoplasm Grading; Prostatectomy; Necrosis
PubMed: 35472669
DOI: 10.5858/arpa.2021-0346-OA -
Technology in Cancer Research &... 2023To build a combined model that integrates clinical data, contrast-enhanced ultrasound, and magnetic resonance perfusion-weighted imaging-based radiomics for predicting...
OBJECTIVE
To build a combined model that integrates clinical data, contrast-enhanced ultrasound, and magnetic resonance perfusion-weighted imaging-based radiomics for predicting the possibility of biochemical recurrence of prostate carcinoma and develop a nomogram tool.
METHOD
We retrospectively analyzed the clinical, ultrasound, and magnetic resonance imaging data of 206 patients pathologically confirmed with prostate carcinoma and receiving radical prostatectomy at Xiangyang No. 1 People's Hospital from February 2015 to August 2021. Based on one to 7 years of follow-up (prostate specific antigen [PSA] level≥0.2 ng/mL, indicative of prostate carcinoma-biochemical recurrence), the patients were divided into biochemical recurrence group (n = 77) and normal group (n = 129). The training and testing sets were formed by dividing the patients at a 7:3 ratio. In training set, The magnetic resonance perfusion-weighted imaging-based radiomics radscore was generated using lasso regression. Several predictive models were built based on the patients' clinical imaging data. The predictive efficacy (area under the curve) of these models was compared using the MedCalc software. The decision curve analysis was conducted using the R to compare the net benefit. Finally, an external validation was carried out on the testing set, and the nomogram tool was developed for predicting prostate carcinoma-biochemical recurrence.
RESULT
The univariate analysis confirmed that Tumor diameter, tumor node metastasis classification stage of tumor, lymph node metastasis or distance metastasis, Gleason grade, preoperative PSA, ultrasound (peak intensity, arrival time, and elastography grade), and magnetic resonance imaging-radscore1/2 were predictors of prostate carcinoma-biochemical recurrence. On the training set, the combined model based on the above factors had the highest predictive efficacy for prostate carcinoma-biochemical recurrence (area under the curve: 0.91; odds ratio 0.02, 95% confidence interval: 0.85-0.95). The predictive performance of the combined model was significantly higher than that of the model based on general clinical data (area under the curve: 0.74; odds ratio 0.04, 95% confidence interval: 0.67-0.81, < .05), contrast-enhanced ultrasound (area under the curve: 0.61; odds ratio 0.05 95% confidence interval: 0.53-0.69, < .05), and the magnetic resonance imaging-based radiomics model (area under the curve: 0.85; odds ratio 0.03, 95% confidence interval: 0.78-0.91, = .01). The decision curve analysis also indicated the maximum net benefit derived from the combined model, which agreed with the validation results on the testing set. The nomogram tool developed based on the combined model achieved a good performance in clinical applications.
CONCLUSION
The magnetic resonance imaging texture parameters extracted by magnetic resonance perfusion-weighted imaging Lasso regression could help increase the accuracy of the predictive model. The combined model and the nomogram tool provide support for the clinical screening of the populations at a risk for biochemical recurrence.
Topics: Male; Humans; Prostate; Prostate-Specific Antigen; Retrospective Studies; Prostatic Neoplasms; Magnetic Resonance Imaging; Perfusion; Carcinoma
PubMed: 37016971
DOI: 10.1177/15330338231166766 -
European Urology Jul 2023The optimal management for men with prostate cancer (PCa) with unconventional histology (UH) is unknown. The outcome for these cancers might be worse than for...
Impact of Epithelial Histological Types, Subtypes, and Growth Patterns on Oncological Outcomes for Patients with Nonmetastatic Prostate Cancer Treated with Curative Intent: A Systematic Review.
CONTEXT
The optimal management for men with prostate cancer (PCa) with unconventional histology (UH) is unknown. The outcome for these cancers might be worse than for conventional PCa and so different approaches may be needed.
OBJECTIVE
To compare oncological outcomes for conventional and UH PCa in men with localized disease treated with curative intent.
EVIDENCE ACQUISITION
A systematic review adhering to the Referred Reporting Items for Systematic Reviews and Meta-Analyses was prospectively registered on PROSPERO (CRD42022296013) was performed in July 2021.
EVIDENCE SYNTHESIS
We screened 3651 manuscripts and identified 46 eligible studies (reporting on 1 871 814 men with conventional PCa and 6929 men with 10 different PCa UHs). Extraprostatic extension and lymph node metastases, but not positive margin rates, were more common with UH PCa than with conventional tumors. PCa cases with cribriform pattern, intraductal carcinoma, or ductal adenocarcinoma had higher rates of biochemical recurrence and metastases after radical prostatectomy than for conventional PCa cases. Lower cancer-specific survival rates were observed for mixed cribriform/intraductal and cribriform PCa. By contrast, pathological findings and oncological outcomes for mucinous and prostatic intraepithelial neoplasia (PIN)-like PCa were similar to those for conventional PCa. Limitations of this review include low-quality studies, a risk of reporting bias, and a scarcity of studies that included radiotherapy.
CONCLUSIONS
Intraductal, cribriform, and ductal UHs may have worse oncological outcomes than for conventional and mucinous or PIN-like PCa. Alternative treatment approaches need to be evaluated in men with these cancers.
PATIENT SUMMARY
We reviewed the literature to explore whether prostate cancers with unconventional growth patterns behave differently to conventional prostate cancers. We found that some unconventional growth patterns have worse outcomes, so we need to investigate if they need different treatments. Urologists should be aware of these growth patterns and their clinical impact.
Topics: Humans; Male; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms
PubMed: 37117107
DOI: 10.1016/j.eururo.2023.03.014 -
Oncogene Jun 2023Prostate cancer (PCa), the second leading cause of death in American men, includes distinct genetic subtypes with distinct therapeutic vulnerabilities. The DACH1 gene...
Prostate cancer (PCa), the second leading cause of death in American men, includes distinct genetic subtypes with distinct therapeutic vulnerabilities. The DACH1 gene encodes a winged helix/Forkhead DNA-binding protein that competes for binding to FOXM1 sites. Herein, DACH1 gene deletion within the 13q21.31-q21.33 region occurs in up to 18% of human PCa and was associated with increased AR activity and poor prognosis. In prostate OncoMice, prostate-specific deletion of the Dach1 gene enhanced prostatic intraepithelial neoplasia (PIN), and was associated with increased TGFβ activity and DNA damage. Reduced Dach1 increased DNA damage in response to genotoxic stresses. DACH1 was recruited to sites of DNA damage, augmenting recruitment of Ku70/Ku80. Reduced Dach1 expression was associated with increased homology directed repair and resistance to PARP inhibitors and TGFβ kinase inhibitors. Reduced Dach1 expression may define a subclass of PCa that warrants specific therapies.
Topics: Male; Humans; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Prostate; DNA Damage; Transforming Growth Factor beta; Eye Proteins; Transcription Factors
PubMed: 37095257
DOI: 10.1038/s41388-023-02668-9