Publications by authors named "Kenneth Iczkowski"

Objectives: Urothelial carcinoma in situ (CIS) with early papillary formation is terminology sometimes used to suggest incipient high-grade papillary urothelial carcinoma (PUC) but may lead to confusion between true CIS and lateral flat spread of PUC.

Methods: It remains unclear how pathologists and urologists interpret this scenario, so a survey was circulated to 68 pathologists (group 1 = 28 academic genitourinary pathologists; group 2 = 17 pathologists with a self-reported genitourinary focus; group 3 = 23 pathologists self-reported as not genitourinary specialists) and 32 urologists.

Results: Regarding atypical urothelial lesions that appear mainly flat but contain possible papillae, group 3 was more likely to label this as CIS compared with groups 1 and 2 (35% for group 3 vs 13% for groups 1 and 2), while groups 1 and 2 more often adopted another descriptive diagnosis, such as "CIS with early papillary features" (38% for groups 1 and 2 vs 13% for group 3).

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  • - The study aimed to assess how pathologists report tumor content in prostate cancer biopsies and evaluate consistency among them using 10 standardized cases.
  • - A survey of 304 pathologists revealed that most report tumor extent as a percentage, but there is significant variability in how they calculate these percentages.
  • - The findings indicate high interobserver variability, especially with percentage reporting, suggesting that using absolute measures of tumor content could provide more consistent results for patient prognosis.
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Unlabelled: It is imperative to identify patients with prostate cancer (PCa) who will benefit from androgen receptor signaling inhibitors that can impact quality of life upon prolonged use. Using our extensively-validated artificial-intelligence technique: cellular morphometric biomarker via machine learning (CMB-ML), we identified 13 CMBs from whole slide images of needle biopsies from the trial specimens ( NCT02430480 , n=37) that accurately predicted response to neoadjuvant androgen deprivation therapy (NADT) (AUC: 0.980).

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  • A significant portion of prostate cancer cases may have a hereditary link, prompting a study into germline pathogenic variants among patients.
  • Among 160 prostate cancer patients tested, 12% were found to have pathogenic variants in various genes, with no notable differences in clinicopathologic characteristics between those with and without these variants.
  • The study highlighted that patients with a family history of cancer were more likely to possess these genetic variants, suggesting a need for further research with larger samples to explore the connections between genetic and clinical data.
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The purpose of this study was to assess the efficacy, specificity, and predictive value of a newly discovered biomarker, Zinc finger-like1 protein (referred to as neuroendocrine marker, NEM) for the detection of prostate cancer (PCa). We retrospectively analyzed banked plasma samples from 508 men, with a median age of 67 years (range 48-97), to compare the performance of NEM and PSA in predicting subsequent histologic PCa. The cohort consisted of four groups of patients visiting a urology clinic: (1) patients not diagnosed with either benign prostatic disease or prostate cancer (PCa) were defined as normal; (2) patients diagnosed with benign hyperplasia (BPH) but not PCa; (3) patients with confirmed PCa; and (4) patients with cancer other than PCa.

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  • * The survey received an 85% response rate from 98 uropathologists, revealing strong agreement on distinguishing between luminal and basal UC types, but varied opinions on the importance of certain genetic tests like FGFR3 and TERT promoter mutations.
  • * Most uropathologists acknowledged the aggressive nature of tumors with micropapillary features and favored further evaluation and specific molecular testing for aggressive subtypes, indicating a need for improved consensus in UC classification and treatment strategies.
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The androgen receptor (AR) is the main driver in the development of castration-resistant prostate cancer, where the emergence of AR splice variants leads to treatment-resistant disease. Through detailed molecular studies of the marine alkaloid manzamine A (MA), we identified transcription factor E2F8 as a previously unknown regulator of AR transcription that prevents AR synthesis in prostate cancer cells. MA significantly inhibited the growth of various prostate cancer cell lines and was highly effective in inhibiting xenograft tumor growth in mice without any pathophysiological perturbations in major organs.

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Background: Vasculature plays a crucial role in the progression of prostate cancer (PC). Changes to the prostatic native vessels have not been studied since 2000 when Garcia et al. demonstrated marked media hypercellularity and increased artery thickness in prostatic native arteries within PC.

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Androgen receptor (AR) drives prostate cancer (PC) growth and progression, and targeting AR signaling is the mainstay of pharmacological therapies for PC. Resistance develops relatively fast as a result of refueled AR activity. A major gap in the field is the lack of understanding of targetable mechanisms that induce persistent AR expression in castrate-resistant PC (CRPC).

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Aims: Pre-surgical risk classification tools for prostate cancer have shown better patient stratification with the addition of cribriform pattern 4 (CC) and intraductal prostatic carcinoma (IDC) identified in biopsies. Here, we analyse the additional prognostic impact of CC/IDC observed in prostatectomies using Cancer of Prostate Risk Assessment post-surgical (CAPRA-S) stratification.

Methods: A retrospective cohort of treatment-naïve radical prostatectomy specimens from three North American academic institutions (2010-2018) was assessed for the presence of CC/IDC.

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Prostate adenocarcinoma is a common malignancy associated with a significant morbidity and mortality. In both prostate biopsies and radical prostatectomy specimens Gleason scoring informs both treatment and outcome prediction. The current convention is that in needle biopsies, Gleason patterns 3, 4 and 5 are considered to be malignant.

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Prostate cancer is the most commonly diagnosed cancer in men, accounting for 27% of the new male cancer diagnoses in 2022. If organ-confined, removal of the prostate through radical prostatectomy is considered curative; however, distant metastases may occur, resulting in a poor patient prognosis. This study sought to determine whether quantitative pathomic features of prostate cancer differ in patients who biochemically experience biological recurrence after surgery.

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Prostate cancer (PCa) is the most diagnosed non-cutaneous cancer in men. Despite therapies such as radical prostatectomy, which is considered curative, distant metastases may form, resulting in biochemical recurrence (BCR). This study used radiomic features calculated from multi-parametric magnetic resonance imaging (MP-MRI) to evaluate their ability to predict BCR and PCa presence.

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  • * A consensus conference in 2022 revealed that around 40% of pathologists do not regularly report T1 subcategories in bladder cancer diagnoses, highlighting a significant variability in practice.
  • * Most attendees supported the routine reporting of T1 subcategories, with semiquantitative methods being preferred over traditional histoanatomic approaches, though many had no strong preference for either method.
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Background: This study aimed to understand the differential levels of inflammatory chemokines in association with higher prostate cancer incidence and mortality in African American (AA) men than in Caucasians (CA).

Methods: The authors used a chemokine assay to simultaneously measure 40 chemokines and cytokines levels in the serum of preoperative prostate cancer patients and healthy controls of AA and CA races. Selected chemokines (CXCL2, CXCL5, and CCL23) serum level was validated in 211 serum samples from prostate cancer patients and healthy controls.

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Background: Pretreatment stratification tools can help in clinical decision making in prostate cancer. To date, none incorporates well-established routinely reported adverse prognostic pathologic features such as intraductal carcinoma of prostate (IDC) or cribriform pattern 4 (CC).

Objective: To assess the impact of addition of CC and/or IDC on the Cancer of Prostate Risk Assessment (CAPRA) and National Cancer Comprehensive Network (NCCN) tools for predicting biochemical recurrence free survival (BCR-FS) and event-free survival (EFS) across multiple patient cohorts.

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Purpose: Digital pathology is becoming an increasingly popular area of advancement in both research and clinically. Pathologists are now able to manage and interpret slides digitally, as well as collaborate with external pathologists with digital copies of slides. Differences in slide scanners include variation in resolution, image contrast, and optical properties, which may influence downstream image processing.

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  • * DACH1 gene deletion, found in up to 18% of PCa cases, correlates with higher activity of the androgen receptor (AR) and poor patient outcomes, as seen in studies involving prostate OncoMice.
  • * The loss of DACH1 expression results in increased DNA damage and resistance to certain cancer therapies (like PARP inhibitors), suggesting that this alteration may indicate a specific subclass of PCa that could benefit from targeted treatment strategies.
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One in eight men will be affected by prostate cancer (PCa) in their lives. While the current clinical standard prognostic marker for PCa is the Gleason score, it is subject to inter-reviewer variability. This study compares two machine learning methods for discriminating between cancerous regions on digitized histology from 47 PCa patients.

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Prostate‑derived calcitonin (CT) and its receptor induce tumorigenicity and increase metastatic potential of prostate cancer (PC). CT‑inducible genes in human prostate were identified by subtraction hybridization. Among these genes, zinc finger protein like 1 (ZFPL1) protein was interesting since it was abundantly expressed in malignant prostates but was almost absent in benign prostates.

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Prostate cancer (PCa), the second leading cause of death in American men, includes distinct genetic subtypes with distinct therapeutic vulnerabilities. The gene encodes a winged helix/Forkhead DNA-binding protein that competes for binding to FOXM1 sites. Herein, gene deletion within the 13q21.

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Aims: There is strong evidence that cribriform morphology indicates a worse prognosis of prostatic adenocarcinoma. Our aim was to investigate its interobserver reproducibility in prostate needle biopsies.

Methods And Results: A panel of nine prostate pathology experts from five continents independently reviewed 304 digitised biopsies for cribriform cancer according to recent International Society of Urological Pathology criteria.

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