High-Grade Prostatic Intraepithelial Neoplasia

Klink, Joseph C.; Miocinovic, Ranko; Galluzzi, Cristina Magi; Klein, Eric A.

doi:10.4111/kju.2012.53.5.297

Cited by 10 publications

(8 citation statements)

References 60 publications

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“…However, there was a great range of miR-125b levels in BPH cells as evident by the large standard deviation. PIN is considered to be a precursor for the development of prostate carcinoma [ 34 , 35 ]. Many of the genetic changes that drive prostate cancer occur early in pathogenesis and are evident in PIN cells.…”

Section: Resultsmentioning

confidence: 99%

Dual Action of miR-125b As a Tumor Suppressor and OncomiR-22 Promotes Prostate Cancer Tumorigenesis

et al. 2015

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MicroRNAs (miRs) are a novel class of small RNA molecules, the dysregulation of which can contribute to cancer. A combinatorial approach was used to identify miRs that promote prostate cancer progression in a unique set of prostate cancer cell lines, which originate from the parental p69 cell line and extend to a highly tumorigenic/metastatic M12 subline. Together, these cell lines are thought to mimic prostate cancer progression in vivo. Previous network analysis and miR arrays suggested that the loss of hsa-miR-125b together with the overexpression of hsa-miR-22 could contribute to prostate tumorigenesis. The dysregulation of these two miRs was confirmed in human prostate tumor samples as compared to adjacent benign glandular epithelium collected through laser capture microdissection from radical prostatectomies. In fact, alterations in hsa-miR-125b expression appeared to be an early event in tumorigenesis. Reverse phase microarray proteomic analysis revealed ErbB2/3 and downstream members of the PI3K/AKT and MAPK/ERK pathways as well as PTEN to be protein targets differentially expressed in the M12 tumor cell compared to its parental p69 cell. Relevant luciferase+3’-UTR expression studies confirmed a direct interaction between hsa-miR-125b and ErbB2 and between hsa-miR-22 and PTEN. Restoration of hsa-miR-125b or inhibition of hsa-miR-22 expression via an antagomiR resulted in an alteration of M12 tumor cell behavior in vitro. Thus, the dual action of hsa-miR-125b as a tumor suppressor and hsa-miR-22 as an oncomiR contributed to prostate tumorigenesis by modulations in PI3K/AKT and MAPK/ERK signaling pathways, key pathways known to influence prostate cancer progression.

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Section: Resultsmentioning

confidence: 99%

Dual Action of miR-125b As a Tumor Suppressor and OncomiR-22 Promotes Prostate Cancer Tumorigenesis

et al. 2015

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“…Discovery of hgpin comes by invasive extraction of a biopsy sample taken because of suspicion for pca 4 , making the experience of the biopsied men much more similar to that of preoperative pca patients than to that of men with elevated psa and no biopsy. Given the semantic association between "neoplasm" and "tumour" (as occurs with dcis 41 ), hgpin can also carry the connotation of cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Approximately 115,000 cases of hgpin are diagnosed each year in North America 6,7 . Diagnosis of hgpin has been found to be highly predictive of pca 4,8 . Approximately one third of men who test negative for cancer but positive for hgpin upon prostate biopsy eventually develop prostate adenocarcinoma 8,9 .…”

Section: Introductionmentioning

confidence: 99%

“…Identification of high-grade prostatic intraepithelial neoplasia (hgpin) on prostate biopsy has also been associated with an elevated risk of pca 4 . High-grade prostatic intraepithelial neoplasia is a premalignant condition characterized by the presence of aberrant cells, which are detected by histopathologic examination of a biopsy specimen 5 .…”

Section: Introductionmentioning

confidence: 99%

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Risk Perception and Psychological Morbidity in Men at Elevated Risk for Prostate Cancer

et al. 2015

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Objective As prostate-specific antigen (psa) makes prostate cancer (pca) screening more accessible, more men are being identified with conditions that indicate high risk for developing pca, such as elevated psa and high-grade intraepithelial neoplasia (hgpin). In the present study, we assessed psychological well-being and risk perception in individuals with those high-risk conditions.Methods A questionnaire consisting of a psychological symptom survey, a trait risk-aversion survey, and a cancerspecific risk perception survey was administered to 168 patients with early-stage localized pca and 69 patients at high risk for pca (n = 16 hgpin, n = 53 psa > 4 ng/mL). Analysis of variance was used to examine differences in psychological well-being and appraisal of risk between the groups. ResultsCompared with the pca group, the high-risk group perceived their risk of dying from something other than pca to be significantly lower (p = 0.007). However, pca patients reported significantly more clinically important psychological symptoms. ConclusionsThe identification of prostate conditions that predict progression to cancer might not result in the psychological symptoms commonly experienced by pca patients, but does appear to be related to a distorted perception of the disease's mortal risk. Patients with pca experience reduced psychological well-being, but better understand the risks of pca recurrence and death. Education on the risks and outcomes of pca can help at-risk men to view health assessments with reduced worry.

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“…In terms of biological variability, the study does not demonstrate performance on a common diagnostic entity-high grade prostatic intraepithelial neoplasia (HGPIN). However, HGPIN represents 4-16% of prostate needle biopsies and can mimic the appearance of prostate cancer [40][41][42] , and therefore could be expected to reduce the specificity of such a system. The work of Campanella et al additionally was unprecedented in terms of image variability covered-it includes a large dataset encompassing slides prepped in 44 countries, representing a degree of variability in staining and tissue preparation characteristics which previous studies have lacked.…”

mentioning

confidence: 99%

Tailored for Real-World: A Whole Slide Image Classification System Validated on Uncurated Multi-Site Data Emulating the Prospective Pathology Workload

Ianni¹,

Soans²,

Sankarapandian³

et al. 2020

Sci Rep

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Standard of care diagnostic procedure for suspected skin cancer is microscopic examination of hematoxylin & eosin stained tissue by a pathologist. Areas of high inter-pathologist discordance and rising biopsy rates necessitate higher efficiency and diagnostic reproducibility. We present and validate a deep learning system which classifies digitized dermatopathology slides into 4 categories. The system is developed using 5,070 images from a single lab, and tested on an uncurated set of 13,537 images from 3 test labs, using whole slide scanners manufactured by 3 different vendors. The system's use of deep-learning-based confidence scoring as a criterion to consider the result as accurate yields an accuracy of up to 98%, and makes it adoptable in a real-world setting. Without confidence scoring, the system achieved an accuracy of 78%. We anticipate that our deep learning system will serve as a foundation enabling faster diagnosis of skin cancer, identification of cases for specialist review, and targeted diagnostic classifications.Every year in the United States, 12 million skin lesions are biopsied 1 , with over 5 million new skin cancer cases diagnosed 2 . After a skin lesion is biopsied, the tissue is fixed, embedded, sectioned, and stained with hematoxylin and eosin (H&E) on glass slides, ultimately to be examined under microscope by a dermatologist, general pathologist or dermatopathologist who provides a diagnosis for each tissue specimen. Owing to the large variety of over 500 distinct skin pathologies 3 and the severe consequences of a critical misdiagnosis 4 , diagnosis in dermatopathology demands specialized training and education. Although the inter-observer concordance rate in dermatopathology is estimated to be between 90 and 95% 5,6 , there are some distinctions which present frequent disagreement among pathologists, such as in the case of melanoma vs. melanocytic nevi 7-11 . Any system which could improve diagnostic accuracy provides obvious benefits for dermatopathology labs and patients; however, there are substantial benefits also to improving the distribution of pathologists' workloads 12-14 . This can reduce diagnostic turnaround times in several scenarios. For example, when skin biopsies are interpreted initially by a dermatologist or a general pathologist, prior to referral to a dermatopathologist, it can result in a delay of days, sometimes in critical cases. In another common scenario, additional staining is required to identify characteristics of the tissue not captured by standard H&E staining. If those additional stains are not ordered early enough, there can be further delays to diagnosis. An intelligent system to distribute pathology workloads could alleviate some of these bottlenecks in lab workflows. The rise in adoption of digital pathology 1,15 provides an opportunity for the use of deep learning-based methods for closing these gaps in diagnostic reliability and efficiency 16,17 .

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High-Grade Prostatic Intraepithelial Neoplasia

Cited by 10 publications

References 60 publications

Dual Action of miR-125b As a Tumor Suppressor and OncomiR-22 Promotes Prostate Cancer Tumorigenesis

Dual Action of miR-125b As a Tumor Suppressor and OncomiR-22 Promotes Prostate Cancer Tumorigenesis

Risk Perception and Psychological Morbidity in Men at Elevated Risk for Prostate Cancer

Tailored for Real-World: A Whole Slide Image Classification System Validated on Uncurated Multi-Site Data Emulating the Prospective Pathology Workload

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