Context.—: Cytologic-histologic correlation (CHC) is a Clinical Laboratory Improvement Amendments-mandated requirement for gynecologic cytology, but no similar requirement exists for nongynecologic cytology. This study presents the findings from a College of American Pathologists survey of nongynecologic cytology practice patterns.
View Article and Find Full Text PDFBackground: The use of cell block (CB) preparation is underused in urine cytology (UC) and varies among hospitals. In addition to confirming a diagnosis, CBs can be useful in cases of metastatic disease, diagnoses requiring immunohistochemical (IHC) staining, and for ancillary studies. The role of this study is to examine the performance of CBs for UC at three affiliated teaching hospitals.
View Article and Find Full Text PDFBackground: The micropapillary variant of urothelial carcinoma (MPVUC) is rare and aggressive. Surgical specimens often show atypical micro-clusters (AMCs) of cells with hyperchromatic, pyknotic, peripheral, irregular nuclei with variable nuclear to cytoplasmic ratios. We reviewed urinary tract cytology (UTC) from patients with MPVUC and hypothesized that AMCs would be present similar to those in surgical specimens.
View Article and Find Full Text PDFContext.—: The College of American Pathologists (CAP) updated the Laboratory Accreditation Program Cytopathology Checklist to assist laboratories in meeting and exceeding the Clinical Laboratory Improvement Amendments standards for gynecologic cytologic-histologic correlation (CHC).
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Introduction: Distinguishing between low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL) can be difficult on certain Papanicolaou (Pap) tests, hindering interobserver concordance. We investigated the variables influencing the interpretation of LSIL versus HSIL in Pap test slides rejected from the College of American Pathologists PAP education program.
Materials And Methods: Eleven cytologists, who were unaware of the reference interpretation, examined 21 Pap slides (11 submitted as LSIL and 10 as HSIL) rejected from the PAP education program and recorded the number of LSIL cells, HSIL cells, keratinized dysplastic cells, LSIL clusters with mixed HSIL cells, atypical squamous metaplasia, atypical glandular cells, the presence of inflammation or infectious organisms, and the overall interpretation (LSIL or HSIL).
Catechol-estrogens can cause genetic mutations and to counteract their oncogenicity, the catechol-O-methyltransferase (COMT) gene is capable of neutralizing these reactive compounds. In this study, we determined the functional effects and regulation of COMT in prostate cancer. Both the Cancer Genome Atlas (TCGA) and immunohistochemical analysis of clinical specimens demonstrated a reduction of COMT expression in prostate cancer.
View Article and Find Full Text PDFMetastasis is the leading cause of mortality from kidney cancer, and understanding the underlying mechanism of this event will provide better strategies for its management. Here we investigated the biological, functional, and clinical significance of lncTCL6 and its interacting miR-155 in clear cell renal cell carcinoma (ccRCC). We employed a comprehensive approach to investigate the lncTCL6-miR-155-Src/Akt-mediated epithelial-to-mesenchymal transition (EMT) pathway as a novel regulatory mechanism in ccRCC progression.
View Article and Find Full Text PDFTherapy-induced neuroendocrine prostate cancer (NEPC), an extremely aggressive variant of castration-resistant prostate cancer (CRPC), is increasing in incidence with the widespread use of highly potent androgen receptor (AR)-pathway inhibitors (APIs) such as Enzalutamide (ENZ) and Abiraterone and arises via a reversible trans-differentiation process, referred to as neuroendocrine differentiation (NED). The molecular basis of NED is not completely understood leading to a lack of effective molecular markers for its diagnosis. Here, we demonstrate for the first time, that lineage switching to NE states is accompanied by key miRNA alterations including downregulation of miR-106a~363 cluster and upregulation of miR-301a and miR-375.
View Article and Find Full Text PDFThe molecular heterogeneity of renal cell carcinoma (RCC) complicates the therapeutic interventions for advanced metastatic disease and thus its management remains a significant challenge. This study investigates the role of the lncRNA CDKN2B-AS1 and miR-141-3p interactions in the progression and metastasis of kidney cancer. Human renal cancer cell lines (ACHN and Caki1), normal RPTEC cells, tissue cohorts, and a series of in vitro assays and in vivo mouse model were used for this study.
View Article and Find Full Text PDFHepatocellular carcinoma (HCC) is a highly heterogeneous liver cancer with significant male biases in incidence, disease progression, and outcomes. Previous studies have suggested that genes on the Y chromosome could be expressed and exert various male-specific functions in the oncogenic processes. In particular, the RNA-binding motif on the Y chromosome (RBMY) gene is frequently activated in HCC and postulated to promote hepatic oncogenesis in patients and animal models.
View Article and Find Full Text PDFNon-invasive assessment of the biological aggressiveness of prostate cancer (PCa) is needed for men with localized disease. Hyperpolarized (HP) C magnetic resonance (MR) spectroscopy is a powerful approach to image metabolism, specifically the conversion of HP [1-C]pyruvate to [1-C]lactate, catalyzed by lactate dehydrogenase (LDH). Significant increase in tumor lactate was measured in high-grade PCa relative to benign and low-grade cancer, suggesting that HP C MR could distinguish low-risk (Gleason score ≤3 + 4) from high-risk (Gleason score ≥4 + 3) PCa.
View Article and Find Full Text PDFAblation of androgen receptor (AR) signaling by androgen deprivation is the goal of the first line of therapy for prostate cancer that initially results in cancer regression. However, in a significant number of cases, the disease progresses to advanced, castration-resistant prostate cancer (CRPC), which has limited therapeutic options and is often aggressive. Distant metastasis is mostly observed at this stage of the aggressive disease.
View Article and Find Full Text PDFPurpose: Neuroendocrine prostate cancer (NEPC), an aggressive variant of castration-resistant prostate cancer (CRPC), often emerges after androgen receptor-targeted therapies such as enzalutamide or , via trans-differentiation process of neuroendocrine differentiation. The mechanistic basis of neuroendocrine differentiation is poorly understood, contributing to lack of effective predictive biomarkers and late disease recognition. The purpose of this study was to examine the role of novel proneural it-ct-nc-domain transcription factors (TF) in NEPC and examine their potential as noninvasive predictive biomarkers.
View Article and Find Full Text PDFContext.—: The Paris System for Reporting Urinary Cytology has been disseminated since its inception in 2013; however, the daily practice patterns of urinary tract cytopathology are not well known.
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Prostate cancer incidence and mortality rates are higher in African-American (AA) than in European-American (EA) men. The main objective of this study was to elucidate the role of miR-130b as a contributor to prostate cancer health disparity in AA patients. We also determined whether miR-130b is a prognostic biomarker and a new therapeutic candidate for AA prostate cancer.
View Article and Find Full Text PDFPurpose: Image-guided prostate biopsies are routinely acquired in the diagnosis and treatment monitoring of prostate cancer, yielding useful tissue for identifying metabolic biomarkers and therapeutic targets. We developed an optimized biopsy tissue culture protocol in combination with [1,6- C ]glucose labeling and quantitative high-resolution NMR to measure glycolysis and tricarboxcylic acid (TCA) cycle activity in freshly acquired living human prostate biopsies.
Methods: We acquired 34 MRI-ultrasound fusion-guided prostate biopsies in vials on ice from 22 previously untreated patients.
The prostate cancer (PCa) genome is characterized by deletions of chromosome 8p21-22 region that increase significantly with tumor grade and are associated with poor prognosis. We proposed and validated a novel, paradigm-shifting hypothesis that this region is associated with a set of microRNA genes-miR-3622, miR-3622b, miR-383-that are lost in PCa and play important mechanistic roles in PCa progression and metastasis. Extending our hypothesis, in this study, we evaluated the role of a microRNA gene located in chromosome 8p-miR-4288-by employing clinical samples and cell lines.
View Article and Find Full Text PDFBackground: Intra-procedural assessment of touch imprint (TI) cytology from needle core biopsies (NCB) is used to ensure sample adequacy and to provide immediate diagnosis in various settings. We aimed to survey laboratories for current practices on the use of cytology with NCB.
Methods: A voluntary supplemental questionnaire including questions on demographics, personnel involved, sites, accessioning, and reporting was sent with the College of American Pathologists (CAP) 2015 Non gynecologic Cytopathology Education Program to survey practices of cytologic assessment of NCB.
Background: The Paris System for Reporting Urinary Cytology (TPS) published in 2016 provides a standardized approach to evaluating urine cytology. In the authors' practice, a TPS-like approach was adopted in 2012 using similarly defined cytologic criteria and correlating cystoscopic findings, and they also began incorporating the use of cell block (CB) material. The objective of the current study was to assess whether this TPS-like approach with the use of CB, as well as direct implementation of TPS, improved the diagnostic value of urine cytology.
View Article and Find Full Text PDFContext.—: Obtaining diagnostic concordance for squamous intraepithelial lesions in cytology can be challenging.
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Cytochrome P450 1B1 (CYP1B1) converts xenobiotics to carcinogens and how lifestyle choices may interact with CYP1B1 polymorphisms and affect prostate cancer risk was assessed. Blood genomic DNA from a Caucasian population was analysed at polymorphic sites of the 5' untranslated region of CYP1B1 using TaqMan genotyping assays. Overall, drinker status and minor alleles at rs2551188, rs2567206 and rs10175368 were associated with prostate cancer.
View Article and Find Full Text PDFThe molecular heterogeneity of clear cell renal carcinoma (ccRCC) makes prediction of disease progression and therapeutic response difficult. Thus, this report investigates the functional significance, mechanisms of action, and clinical utility of miR-182-5p and metastasis-associated lung adenocarcinoma transcript 1 (), a long noncoding RNA (lncRNA), in the regulation of kidney cancer using human kidney cancer tissues as well as and model systems. Profiling of miR-182-5p and in human renal cancer cells and clinical specimens was done by quantitative real-time PCR (qPCR).
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