Search Results (36)

Background: Germline alterations in DNA damage repair (DDR) genes represent a clinically important subset of prostate cancer (PCa), but real-world data from Middle Eastern and Turkish populations remain limited. We evaluated the prevalence and clinicopathologic associations of germline DDR variants in a single-center Turkish cohort. Methods: We retrospectively analyzed 122 men with histologically confirmed PCa who underwent germline multigene panel testing. Variants were classified according to ACMG/ClinVar criteria. Patients were grouped as pathogenic/likely pathogenic (P/LP), variants of uncertain significance (VUS), or variant-negative. Patients were grouped as variant-positive (P/LP or VUS/uncategorized) or clinically actionable variant–negative (benign/likely benign or no variant detected). Group comparisons used t-tests, chi-square or Fisher’s exact tests as appropriate. Results: The median age at diagnosis was 65.2 years (mean 64.6 ± 8.78). Overall, 37 patients (30.3%) carried at least one germline variant, including 12 (9.8%) with P/LP alterations and 24 (19.7%) with VUS; one patient (0.8%) harbored an uncategorized variant. The most frequently affected genes were CHEK2 (n = 8), BRCA1 (n = 6), BRCA2 (n = 6), ATM (n = 5), and APC (n = 4). Variant-positive status increased from 10.8% in ISUP 1–2 to 21.6% in ISUP 3 and 76.0% in ISUP 4–5, although this trend was not statistically significant (p = 0.391). Mean age at diagnosis and the prevalence of metastatic disease did not differ between variant-positive and clinically actionable variant–negative patients (64.2 vs. 65.7 years, p = 0.390; 66.7% vs. 64.6%, p = 0.842). Truncating DDR variants (RAD50, BRCA2, MSH3, NBN, CHEK2, ATM) occurred predominantly in ISUP 4–5 tumors. Conclusions: Germline DDR alterations—most notably in BRCA2, CHEK2, and ATM—were present in a substantial subset of Turkish men with PCa and showed a non-significant trend toward clustering in higher-grade disease. The high prevalence of VUS reflects limited genomic annotation in under-represented populations and underscores the need for longitudinal reinterpretation. These data support the clinical value of incorporating germline DDR testing into risk assessment and familial counseling, while larger cohorts integrating somatic profiling are needed to refine genotype–phenotype associations. Full article

Prostate cancer (PCa) diagnosis has historically relied on the prostate-specific antigen (PSA) testing. Although the screening significantly reduces mortality rates, PSA has low specificity with risks of overdiagnosis and overtreatment. These limitations highlight the need for a more accurate diagnostic approach. Emerging technologies, such as artificial intelligence (AI), novel biomarkers, and advanced imaging techniques, offer promising avenues to enhance the accuracy and efficiency of PCa diagnosis and risk stratification. This narrative review comprehensively analyzed the current literature, focusing on new tools aiding PCa diagnosis (AI-driven image interpretation, radiomics, genomic classifiers, biomarkers, and multimodal data integration) with consideration for technical, regulatory, and ethical challenges related to clinical implementation of AI-based technologies. A literature search was performed using the PubMed and MEDLINE databases to identify relevant peer-reviewed articles published in English using the search terms “prostate cancer,” “artificial intelligence,” “machine learning,” “deep learning,” “MRI,” “histopathology,” and “diagnosis.” Articles were selected based on their relevance to AI-assisted diagnostic tools, clinical utility, and performance metrics. In addition, a separate section was developed initially to contextualize the limitations of current PSA-based screening approaches. The reviewed studies showed that AI had significant utility in prostate mpMRI interpretation (lesion detection; Gleason grading) with high accuracy and high reproducibility. For the pathologist, AI-driven algorithms improve the diagnostic accuracy of digital slide evaluation for histologic diagnosis of prostate cancer and automated Gleason score grading. Genomic tools such as the Oncotype DX test, combined with AI, could also allow for tailored and individualized risk prediction. Overall, multimodal models integrating clinical, imaging, and molecular data often outperform traditional PSA-based strategies and reduce unnecessary biopsies. Transition from PSA-centered toward AI-driven, biomarker-supported, and image-enhanced diagnosis marks a critical evolution in PCa diagnosis. Full article

This study presents the development of a quantitative evaluation method utilizing machine vision technology to characterize the extent of body surface damage in largemouth bass (Micropterus salmoides) infected with largemouth bass ranavirus (LMBV). High-resolution, multi-angle images (6000 × 4000 pixels) of the body surface from 239 infected specimens were acquired at a fixed distance of 40 cm using a SONY ILCE-7RM3 digital camera within a GODOX-LST60 softbox. Key parameters, including the number of segmented injury areas, the count of body surface lesions, and the total lesion area, were analyzed. These parameters were integrated through principal component analysis (PCA) to construct a comprehensive damage scoring model. The severity of viral-induced body surface damage was categorized into four grades: uninjured (0), minor injury (1), moderate injury (2), and severe injury (3). Histopathological examination revealed that early-stage infection (grade 1) predominantly exhibited localized hemorrhagic spots in the muscular region of the body side (B/E region) with limited lesion area. In contrast, moderate to severe infections (grades 2–3) were characterized by extensive ulceration, muscle necrosis, and visceral lesions, including hepatic fibrosis and splenic granulomatous formations. Quantitative real-time PCR (qRT-PCR) analysis demonstrated a progressive upregulation of pro-inflammatory cytokines (IL-6, IL-8, TNF-α, CXCL2) in immune organs, concomitant with increased expression of apoptosis-related genes (CASP8, CYC). This study successfully established a rapid and objective quantitative grading system for ranavirus infection, offering a novel technical approach for early diagnosis and precise prevention and control strategies against largemouth bass ranavirus. Full article

Background and Clinical Significance: Prostate cancer (PCa) is among the most commonly diagnosed malignancies in men worldwide. While bone and lymph nodes are the most frequent metastatic sites, prostate cancer cells have the potential to spread to virtually any organ, including the pleura, which is an exceedingly rare initial site of presentation that can mimic mesothelioma or primary lung cancer. Case Presentation: We describe a 77-year-old man who presented with exertional dyspnea and intermittent cough, initially suggesting a cardiopulmonary etiology. Imaging revealed multiple pleural nodules and an extensive right-sided pleural effusion. Despite a borderline serum prostate-specific antigen (PSA) level of 2.91 ng/mL, histopathology and immunohistochemistry of pleural biopsies confirmed metastatic prostate adenocarcinoma. Subsequent imaging identified a PIRADS 5 lesion in the prostate, and a biopsy confirmed ISUP Grade Group 5 disease (Gleason score 4 + 5 = 9). A bone scan showed no skeletal metastases, and a contrast-enhanced CT of the abdomen found no additional metastatic lesions. The patient was started on androgen deprivation therapy followed by abiraterone. This case underscores the diagnostic challenge posed by atypical metastatic presentations of prostate cancer. Low or moderately elevated PSA can obscure suspicion of prostate origin, especially with pleural-based lesions suggestive of mesothelioma. Immunohistochemical markers, including androgen receptors, AMACR, and Prostein, are critical for accurate diagnosis. Conclusions: Clinicians must maintain a high index of suspicion for prostate cancer in older men with unexplained pleural effusions, nodules, or masses, even with low-normal PSA levels. Early recognition and prompt treatment can improve outcomes, despite the rarity and aggressiveness of pleural metastases. Full article

Background: The standard diagnostic approach for prostate cancer (PCa) diagnosis consists of serum prostate-specific antigen (PSA) testing, digital rectal examination (DRE) and image-guided targeted biopsies. Given the invasive nature, potential adverse events and costs associated with these techniques, alternative approaches have been investigated, specifically with serum and urine assays. The work presented here is intended to further validate a novel noninvasive optical technique for PCa detection, targeting the VPAC genomic receptors that are overexpressed on prostate cancer’s malignant cells (MC), in non-DRE voided urine. Methods: Patients (N = 62) who had image-guided biopsy and histologically confirmed localized PCa, and who were scheduled for radical prostatectomy, provided a non-DRE voided urine sample prior to surgery. Urine was cytocentrifuged and cells fixed on a glass slide, incubated with 0.5 μg TP4303 (a receptor-specific fluorophore developed in our laboratory with high affinity for VPAC), excess washed and treated with 4,6-diamidodino-2-phenylindole (DAPI) for nuclear staining. The field of cells on each slide was analyzed using a Zeiss AX10 Observer microscope (20×). The total number of cells and MC were then counted, and the florescent intensity around each MC was measured using Zeiss software. Additionally, non-DRE voided urine samples collected from clinically determined BPH patients (N = 97), were also analyzed similarly. Results: Urine samples from 62 patients were processed and analyzed. Mean PSA levels by Gleason grade (GG) group were 6.5 ± 4.1 ng/mL for GG1 (N = 10), 7.2 ± 3.8 for GG2 (N = 31), 13.2 ± 14.6 for GG3 (N = 13), 6.2 ± 2.2 for GG4 (N = 2) and 50.2 ± 104.9 for GG5 (N = 6). Like the PSA, % MC shed (66.7 ± 27.7) in voided urine and the fluorescent intensity (35.8 ± 5.7) were highest in patients with GG5 prostate cancer. All PCa patients in GG1 to GG5 shed MC in voided urine with increasing % of MC and increasing fluorescence intensity which correlated with the increasing GG for PCa. For BPH, the specificity for the assay was 89.6% (95% CI:81.9–94.9%), PPV was 0.0% and NPV was 100% (95.9% CI, 95.9–100%). Conclusions: These data indicate the following: (i) PCa MC shed in non-DRE voided urine can be detected by targeting VPAC receptors, (ii) MC are shed in non-DRE voided urine with increasing quantity, corresponding to the severity of the disease, and (iii) this non-DRE voided urine optical assay provides a simple, noninvasive, and reliable method for the preliminary detection of PCa with potentially a lower cost than the currently available pre-biopsy detection technologies. Full article

Background/Objectives: High-grade serous carcinomas (HGSCs) are highly heterogeneous tumors, both among patients and within a single tumor. Differences in molecular mechanisms significantly describe this heterogeneity. Four molecular subtypes have been previously described by the Cancer Genome Atlas Consortium: differentiated, immunoreactive, mesenchymal, and proliferative. These subtypes may have varying degrees of progression, relapse-free survival, and overall survival, as well as response to therapy. The precise determination of these subtypes is certainly necessary both for diagnosis and future development of targeted therapies within personalized medicine. Methods: In this study, we analyzed gene expression data based on bulk RNA-seq, scRNA-seq, and spatial transcriptomic data from six cohorts (totaling 535 samples, including 60 single-cell samples). Differential expression analysis was performed using the edgeR package. The KEGG database and GSVA package were used for pathways enrichment analysis. As a predictive model, a deep neural network was created using the keras and tensorflow libraries. Results: We identified 357 differentially expressed genes among the four subtypes: 96 differentiated, 33 immunoreactive, 91 mesenchymal, and 137 proliferative. Based on these, we created OVsignGenes, a neural network model resistant to the effects of platform (test dataset AUC = 0.969). We then ran data from five more cohorts through our model, including scRNA-seq and spatial transcriptomics. Conclusions: Because the differentiated subtype is located at the intersection of the other three subtypes based on PCA and does not have a unique profile of differentially expressed genes or enriched pathways, it can be considered an initiating subtype of tumor that will develop into one of the three other subtypes. Full article

Widespread adoption of mpMRI has led to a decrease in the number of patients requiring prostate biopsies. ⁶⁸Ga-PSMA-11 PET/CT has demonstrated added benefits in identifying csPCa. Integrating the use of these imaging techniques may hold promise for predicting the presence of csPCa without invasive biopsy. A retrospective analysis of 42 consecutive patients who underwent mpMRI, ⁶⁸Ga-PSMA-11 PET/CT, prostatic biopsy, and radical prostatectomy (RP) was carried out. A lesion-based model (n = 122) using prostatectomy histopathology as reference standard was used to analyze the accuracy of ⁶⁸Ga-PSMA-11 PET/CT, mpMRI alone, and both in combination to identify ISUP-grade group ≥ 2 lesions. ⁶⁸Ga-PSMA-11 PET/CT demonstrated greater specificity and positive predictive value (PPV), with values of 73.3% (vs. 40.0%) and 90.1% (vs. 82.2%), while the mpMRI Prostate Imaging Reporting and Data System (PI-RADS) 4–5 had better sensitivity and negative predictive value (NPV): 90.2% (vs. 78.5%) and 57.1% (vs. 52.4%), respectively. When used in combination, the sensitivity, specificity, PPV, and NPV were 74.2%, 83.3%, 93.2%, and 51.0%, respectively. Subgroup analysis of PI-RADS 3, 4, and 5 lesions was carried out. For PI-RADS 3 lesions, ⁶⁸Ga-PSMA-11 PET/CT demonstrated a NPV of 77.8%. For PI-RADS 4–5 lesions, ⁶⁸Ga-PSMA-11 PET/CT achieved PPV values of 82.1% and 100%, respectively, with an NPV of 100% in PI-RADS 5 lesions. A combination of ⁶⁸Ga-PSMA-11 PET/CT and mpMRI improved the radiological diagnosis of csPCa. This suggests that avoidance of prostate biopsy prior to RP may represent a valid option in a selected subgroup of high-risk patients with a high suspicion of csPCa on mpMRI and ⁶⁸Ga-PSMA-11 PET/CT. Full article

N6-methyladenosine (m6A) methylation, a prevalent epitranscriptomic modification, plays a crucial role in regulating mRNA expression, stability, and translation in mammals. M6A regulators have gained attention for their potential implications in tumorigenesis and clinical applications, such as cancer diagnosis and therapeutics. The existing literature predominantly addresses m6A regulators in the context of primary prostate cancer (PCa). However, a notable gap in the knowledge emerges regarding the dynamic expression patterns of these regulators as PCa progresses towards the castration-resistant stage (CRPC). Employing sequential window acquisition of all theoretical mass spectra (SWATH-MS) and RNAseq analysis, we comprehensively profiled the expression of 27 m6A regulators in hormone/androgen-dependent and -independent PCa cell lines, revealing distinct clustering between tumor and adjacent normal prostate tissues. High-grade PCa tumors demonstrated the upregulation of METTL3, RBM15B, and HNRNAPA2B1 and the downregulation of ZC3H13, NUDT21, and FTO. Notably, we identified six m6A regulators associated with PCa survival. Additionally, association analysis of the PCa-associated risk loci in the cancer genome atlas program (TCGA) data unveiled genetic variations near the WTAP, HNRNPA2B1, and FTO genes as significant expression quantitative trait loci. In summary, our study unraveled abnormalities in m6A regulator expression in PCa progression, elucidating their association with PCa risk loci. Considering the heterogeneity within the PCa phenotypes and treatment responses, our findings suggest that prognostic stratification based on m6A regulator expression could enhance PCa diagnosis and prognosis. Full article

This study presents ATR-FTIR (attenuated total reflectance Fourier-transform infrared) spectral analysis of ex vivo oesophageal tissue including all classifications to oesophageal adenocarcinoma (OAC). The article adds further validation to previous human tissue studies identifying the potential for ATR-FTIR spectroscopy in differentiating among all classes of oesophageal transformation to OAC. Tissue spectral analysis used principal component analysis quadratic discriminant analysis (PCA-QDA), successive projection algorithm quadratic discriminant analysis (SPA-QDA), and genetic algorithm quadratic discriminant analysis (GA-QDA) algorithms for variable selection and classification. The variables selected by SPA-QDA and GA-QDA discriminated tissue samples from Barrett’s oesophagus (BO) to OAC with 100% accuracy on the basis of unique spectral “fingerprints” of their biochemical composition. Accuracy test results including sensitivity and specificity were determined. The best results were obtained with PCA-QDA, where tissues ranging from normal to OAC were correctly classified with 90.9% overall accuracy (71.4–100% sensitivity and 89.5–100% specificity), including the discrimination between normal and inflammatory tissue, which failed in SPA-QDA and GA-QDA. All the models revealed excellent results for distinguishing among BO, low-grade dysplasia (LGD), high-grade dysplasia (HGD), and OAC tissues (100% sensitivities and specificities). This study highlights the need for further work identifying potential biochemical markers using ATR-FTIR in tissue that could be utilised as an adjunct to histopathological diagnosis for early detection of neoplastic changes in susceptible epithelium. Full article

The standard procedure for the diagnosis of prostate carcinoma involves the collection of 10–12 systematic biopsies (SBx) from both lobes. MRI-guided targeted biopsies (TBx) from suspicious foci increase the detection rates of clinically significant (cs) PCa. We investigated the extent to which the results of the TBx predicted the tumor board treatment decisions. SBx and TBx were acquired from 150 patients. Risk stratifications and recommendations for interventional therapy (prostatectomy and radiotherapy) or active surveillance were established by interdisciplinary tumor boards. We analyzed how often TBx alone were enough to correctly classify the tumors as well as to indicate interventional therapy and how often the findings of SBx were crucial for therapy decisions. A total of 28/39 (72%) favorable risk tumors were detected in TBx, of which 11/26 (42%) very-low-risk tumors were not detected and 8/13 (62%) low-risk tumors were undergraded. A total of 36/44 (82%) intermediate-risk PCa were present in TBx, of which 4 (9%) were underdiagnosed as a favorable risk tumor. A total of 12/13 (92%) high-risk carcinomas were detected and correctly grouped in TBx. The majority of csPCa were identified by the sampling of TBx alone. The tumor size was underestimated in a proportion of ISUP grade 1 tumors. Systematic biopsy sampling is therefore indicated for the next AS follow-up in these cases. Full article

Usually, after an abnormal level of serum prostate-specific antigen (PSA) or digital rectal exam, men undergo a prostate needle biopsy. However, the traditional sextant technique misses 15–46% of cancers. At present, there are problems regarding disease diagnosis/prognosis, especially in patients’ classification, because the information to be handled is complex and challenging to process. Matrix metalloproteases (MMPs) have high expression by prostate cancer (PCa) compared with benign prostate tissues. To assess the possible contribution to the diagnosis of PCa, we evaluated the expression of several MMPs in prostate tissues before and after PCa diagnosis using machine learning, classifiers, and supervised algorithms. A retrospective study was conducted on 29 patients diagnosed with PCa with previous benign needle biopsies, 45 patients with benign prostatic hyperplasia (BHP), and 18 patients with high-grade prostatic intraepithelial neoplasia (HGPIN). An immunohistochemical study was performed on tissue samples from tumor and non-tumor areas using specific antibodies against MMP -2, 9, 11, and 13, and the tissue inhibitor of MMPs -3 (TIMP-3), and the protein expression by different cell types was analyzed to which several automatic learning techniques have been applied. Compared with BHP or HGPIN specimens, epithelial cells (ECs) and fibroblasts from benign prostate biopsies before the diagnosis of PCa showed a significantly higher expression of MMPs and TIMP-3. Machine learning techniques provide a differentiable classification between these patients, with greater than 95% accuracy, considering ECs, being slightly lower when considering fibroblasts. In addition, evolutionary changes were found in paired tissues from benign biopsy to prostatectomy specimens in the same patient. Thus, ECs from the tumor zone from prostatectomy showed higher expressions of MMPs and TIMP-3 compared to ECs of the corresponding zone from the benign biopsy. Similar differences were found for expressions of MMP-9 and TIMP-3, between fibroblasts from these zones. The classifiers have determined that patients with benign prostate biopsies before the diagnosis of PCa showed a high MMPs/TIMP-3 expression by ECs, so in the zone without future cancer development as in the zone with future tumor, compared with biopsy samples from patients with BPH or HGPIN. Expression of MMP -2, 9, 11, and 13, and TIMP-3 phenotypically define ECs associated with future tumor development. Also, the results suggest that MMPs/TIMPs expression in biopsy tissues may reflect evolutionary changes from prostate benign tissues to PCa. Thus, these findings in combination with other parameters might contribute to improving the suspicion of PCa diagnosis. Full article

Evaluating the aggressiveness of prostate cancer (PCa) is crucial for PCa diagnosis and prognosis. Previously, studies have shown that photoacoustic spectral analysis (PASA) can assess prostate tissue microarchitecture for evaluating the aggressiveness of PCa. In this study, in a transgenic mouse (TRAMP) model of PCa, we utilized methylene blue polyacrylamide nanoparticles (MB PAA NPs) to label the cancer cells in prostate in vivo. MB PAA NPs can specifically target proliferating cancer cells as a contrast agent, allowing photoacoustic (PA) imaging to better detect PCa tumors, and also assessing prostate glandular architecture. With the PA signals from the prostates measured simultaneously by a needle hydrophone and a PA and ultrasound (US) dual-imaging system, we conducted PASA and correlated the quantified spectral parameter slopes with the cancer grading from histopathology. The PASA results from 18 mice showed significant differences between normal and cancer, and also between low-score cancer and high-score cancer. This study in the clinically relevant TRAMP model of PCa demonstrated that PA imaging and PASA, powered by MB PAA NPs that can label the PCa microarchitectures in vivo after systemic administration, can detect PCa and, more importantly, evaluate cancer aggressiveness. Full article

There is still a lack of reliable intraoperative tools for glioma diagnosis and to guide the maximal safe resection of glioma. We report continuing work on the optical biopsy method to detect glioma grades and assess glioma boundaries intraoperatively using the VRR-LRR^TM Raman analyzer, which is based on the visible resonance Raman spectroscopy (VRR) technique. A total of 2220 VRR spectra were collected during surgeries from 63 unprocessed fresh glioma tissues using the VRR-LRR^TM Raman analyzer. After the VRR spectral analysis, we found differences in the native molecules in the fingerprint region and in the high-wavenumber region, and differences between normal (control) and different grades of glioma tissues. A principal component analysis–support vector machine (PCA-SVM) machine learning method was used to distinguish glioma tissues from normal tissues and different glioma grades. The accuracy in identifying glioma from normal tissue was over 80%, compared with the gold standard of histopathology reports of glioma. The VRR-LRR^TM Raman analyzer may be a new label-free, real-time optical molecular pathology tool aiding in the intraoperative detection of glioma and identification of tumor boundaries, thus helping to guide maximal safe glioma removal and adjacent healthy tissue preservation. Full article

We aimed to estimate the total health care costs attributable to prostate cancer (PCa) during care phases by age, cancer stage, tumor grade, and primary treatment in the first year in British Columbia (BC), Canada. Using linked administrative health data, we followed a cohort of men aged ≥ 50 years at diagnosis with PCa between 2010 and 2017 (Cohort 1) from the diagnosis date until the date of death, the last date of observation, or 31 December 2019. Patients who died from PCa after 1 January 2010, were selected for Cohort 2. PCa attributable costs were estimated by comparing costs in patients to matched controls. Cohort 1 (n = 22,672) had a mean age of 69.9 years (SD = 8.9) and a median follow-up time of 5.2 years. Cohort 2 included 6942 patients. Mean PCa attributable costs were the highest during the first year after diagnosis ($14,307.9 [95% CI: $13,970.0, $14,645.8]) and the year before death ($9959.7 [$8738.8, $11,181.0]). Primary treatment with radiation therapy had significantly higher costs each year after diagnosis than a radical prostatectomy or other surgeries in advanced-stage PCa. Androgen deprivation therapy (and/or chemotherapy) had the highest cost for high-grade and early-stage cancer during the three years after diagnosis. No treatment group had the lowest cost. Updated cost estimates could inform economic evaluations and decision-making. Full article

Modern risk stratification of prostate cancer (PCa) allows for prediction of advanced disease with a high level of certainty. We aimed to evaluate a prospective series of patients undergoing radical prostatectomy without prior biopsy based solely on clinical criteria and imaging results. The patients were divided into three groups. Group 1 included 27 patients with: (i) suspicious digital rectal examination, (ii) PSA ≥ 10 ng/mL, (iii) PI-RADS 4/5 on mpMRI, and (iv) high suspicion of PCa on PSMA-PET. Group 2 included six patients who fulfilled criteria i, ii, and iii but did not undergo PSMA-PET imaging. Group 3 included 17 patients with at least one clinical (i or ii) and one imaging (iii or iv) criterion. All of the patients were diagnosed with PCa. Comparison of Group 1 and 2 versus Group 3 showed a significantly higher ratio of locally advanced PCa for Groups 1 and 2 compared to Group 3 (60.6% versus 11.8%, p = 0.005, respectively). Similarly, these patients displayed a significantly higher ratio of aggressive PCa (ISUP grade > 2: 66.7% versus 23.5%, p = 0.027, respectively) and tumor infiltration (median tumor infiltration: 32.5% vs. 15%, p = 0.001, respectively) in the final specimen compared to Group 3. In conclusion, we have shown that radical prostatectomy without prior biopsy is safe in terms of the diagnosis of clinically significant PCa when proper preoperative risk stratification involving mpMRI and PSMA-PET imaging is applied. Full article