Correlation of p53 immunoexpression with DNA ploidy and apoptotic index in subsets of prostate cancer: A marker reiterated in progression and recurrence of prostate cancer

Abstract Background: Prediction of biological behavior in patients of prostate cancer (CaP) is a major challenge as current parameters only partially meet the need for prognostication. p53 as a prognostic indicator has been studied in several human cancers, including breast, lung, and colorectal carcinoma. However, its significance as a predictive biomarker for CaP is less well-studied. Materials and Methods: This study included 125 cases of CaP, 27 cases of prostatic intraepithelial neoplasia and 25 cases of benign prostatic hyperplasia. Immunohistochemical assessment for p53 nuclear protein was performed. Assessment for apoptotic index and DNA ploidy status by flow cytometry were also done. Results: p53 immunoreactivity was low in organ confined CaP cases having Gleason score ≤3 (P < 0.003). More hormone resistant cases 37 (83%) were aneuploid when compared with hormone sensitive cases 26 (33%) (P < 0.005). 93% of p53 positive cases and none of the p53 negative patient were aneuploid suggesting a significant relation between p53 immunoreactivity and aneuploidy. p53 positivity and DNA aneuploidy, independently, were also predictors of progression and relapse. Conclusion: DNA ploidy and p53 positivity go hand in hand and together yield additional prognostic information in CaP. p53 positivity is possibly a late event in carcinogenesis in CaP and a marker of change in biological behavior of CaP.

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Desmin and CD31 immunolabeling for detecting venous invasion of the pancreatobiliary tract cancers

PLoS ONE ◽

10.1371/journal.pone.0242571 ◽

2020 ◽

Vol 15 (11) ◽

pp. e0242571

Author(s):

Junyoung Shin ◽

Laura D. Wood ◽

Ralph H. Hruban ◽

Seung-Mo Hong

Keyword(s):

Disease Free Survival ◽

Venous Invasion ◽

Intraepithelial Neoplasia ◽

Prognostic Indicator ◽

Prognostic Information ◽

Test Set ◽

Poor Prognostic Factor ◽

Tract Cancer ◽

Added Benefit ◽

Validation Set

Although venous invasion (VI) is a poor prognostic factor for patients with pancreatobiliary tract cancers, its histopathologic characteristics have not been well described. We evaluated the patterns of VI and the added benefit provided by CD31, desmin, and dual CD31‒desmin immunolabeling for identification of VI. We included 120 surgically resected pancreatobiliary tract cancer cases—59 cases as a test set with known VI and 61 cases as a validation set without information of VI. VI was classified into three patterns: intraepithelial neoplasia-like (IN-like), conventional, and destructive. Hematoxylin and eosin (H&E) staining and CD31, desmin, and dual CD31‒desmin immunolabeling were performed. Foci number and patterns of VI were compared with the test and validation sets. More foci of VI were detected by single CD31 (P = 0.022) than H&E staining in the test set. CD31 immunolabeling detected more foci of the conventional pattern of VI, and desmin immunolabeling detected more foci of the destructive pattern (all, P < 0.001). Dual CD31‒desmin immunolabeling identified more foci of VI (P = 0.012) and specifically detected more foci of IN-like (P = 0.045) and destructive patterns (P < 0.001) than H&E staining in the validation set. However, dual CD31‒desmin immunolabeling was not helpful for detecting the conventional pattern of VI in the validation set. Patients with VI detected by dual CD31‒desmin immunolabeling had shorter disease-free survival (P <0.001) than those without VI. VI detected by dual CD31‒desmin immunolabeling was a worse prognostic indicator (P = 0.009). More foci of VI could be detected with additional single CD31 or dual CD31‒desmin immunolabeling. The precise evaluation of VI with dual CD31‒desmin immunolabeling can provide additional prognostic information for patients with surgically resected pancreatobiliary tract cancers.

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The combination of DNA ploidy status and PTEN/6q15 deletions to provide strong and independent prognostic information in prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.15_suppl.5027 ◽

2015 ◽

Vol 33 (15_suppl) ◽

pp. 5027-5027

Author(s):

Maximilian Lennartz ◽

Sarah Minner ◽

Martina Kluth ◽

Sophie Brasch ◽

Hilko Wittmann ◽

...

Keyword(s):

Prostate Cancer ◽

Dna Ploidy ◽

Prognostic Information ◽

Ploidy Status

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The Combination of DNA Ploidy Status and PTEN/6q15 Deletions Provides Strong and Independent Prognostic Information in Prostate Cancer

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-15-0635 ◽

2016 ◽

Vol 22 (11) ◽

pp. 2802-2811 ◽

Cited By ~ 14

Author(s):

Maximilian Lennartz ◽

Sarah Minner ◽

Sophie Brasch ◽

Hilko Wittmann ◽

Leonard Paterna ◽

...

Keyword(s):

Prostate Cancer ◽

Dna Ploidy ◽

Prognostic Information ◽

Ploidy Status

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523: Risk of Prostate Cancer on Re-Biopsy Following a Diagnosis of High-Grade Prostatic Intraepithelial Neoplasia (HGPIN) is Related to the Number of Cores Sampled

The Journal of Urology ◽

10.1016/s0022-5347(18)34763-3 ◽

2005 ◽

Vol 173 (4S) ◽

pp. 142-143 ◽

Cited By ~ 1

Author(s):

Mehsati Herawi ◽

Christina Cavallo ◽

Hillel Kahane ◽

Jonathan I. Epstein

Keyword(s):

Prostate Cancer ◽

Intraepithelial Neoplasia ◽

Prostatic Intraepithelial Neoplasia ◽

High Grade

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Glyoxalase 1 Expression as a Novel Diagnostic Marker of High-Grade Prostatic Intraepithelial Neoplasia in Prostate Cancer

Cancers ◽

10.3390/cancers13143608 ◽

2021 ◽

Vol 13 (14) ◽

pp. 3608

Author(s):

Liliana Rounds ◽

Ray B. Nagle ◽

Andrea Muranyi ◽

Jana Jandova ◽

Scott Gill ◽

...

Keyword(s):

Prostate Cancer ◽

Diagnostic Marker ◽

Precancerous Lesion ◽

Immunohistochemical Analysis ◽

Intraepithelial Neoplasia ◽

Prostatic Intraepithelial Neoplasia ◽

Glycolytic Flux ◽

Gleason Grade ◽

High Grade ◽

Glyoxalase 1

Glyoxalase 1 (GLO1) is an enzyme involved in the detoxification of methylglyoxal (MG), a reactive oncometabolite formed in the context of energy metabolism as a result of high glycolytic flux. Prior clinical evidence has documented GLO1 upregulation in various tumor types including prostate cancer (PCa). However, GLO1 expression has not been explored in the context of PCa progression with a focus on high-grade prostatic intraepithelial neoplasia (HGPIN), a frequent precursor to invasive cancer. Here, we have evaluated GLO1 expression by immunohistochemistry in archival tumor samples from 187 PCa patients (stage 2 and 3). Immunohistochemical analysis revealed GLO1 upregulation during tumor progression, observable in HGPIN and PCa versus normal prostatic tissue. GLO1 upregulation was identified as a novel hallmark of HGPIN lesions, displaying the highest staining intensity in all clinical patient specimens. GLO1 expression correlated with intermediate–high risk Gleason grade but not with patient age, biochemical recurrence, or pathological stage. Our data identify upregulated GLO1 expression as a molecular hallmark of HGPIN lesions detectable by immunohistochemical analysis. Since current pathological assessment of HGPIN status solely depends on morphological features, GLO1 may serve as a novel diagnostic marker that identifies this precancerous lesion.

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High KIFC1 expression is associated with poor prognosis in prostate cancer

Medical Oncology ◽

10.1007/s12032-021-01494-x ◽

2021 ◽

Vol 38 (5) ◽

Author(s):

Laurie G. Kostecka ◽

Athen Olseen ◽

KiChang Kang ◽

Gonzalo Torga ◽

Kenneth J. Pienta ◽

...

Keyword(s):

Prostate Cancer ◽

Poor Prognosis ◽

Prognostic Indicator ◽

Tumor Stage ◽

Ploidy Levels ◽

Free Survival ◽

Metastatic Lesions ◽

High Tumor Stage ◽

High Ploidy ◽

Kinesin Family

AbstractKinesins play important roles in the progression and development of cancer. Kinesin family member C1 (KIFC1), a minus end-directed motor protein, is a novel Kinesin involved in the clustering of excess centrosomes found in cancer cells. Recently KIFC1 has shown to play a role in the progression of many different cancers, however, the involvement of KIFC1 in the progression of prostate cancer (PCa) is still not well understood. This study investigated the expression and clinical significance of KIFC1 in PCa by utilizing multiple publicly available datasets to analyze KIFC1 expression in patient samples. High KIFC1 expression was found to be associated with high Gleason score, high tumor stage, metastatic lesions, high ploidy levels, and lower recurrence-free survival. These results reveal that high KIFC1 levels are associated with a poor prognosis for PCa patients and could act as a prognostic indicator for PCa patients as well.

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What is the risk of prostate cancer mortality following negative systematic TRUS-guided biopsies? A systematic review

BMJ Open ◽

10.1136/bmjopen-2020-040965 ◽

2020 ◽

Vol 10 (12) ◽

pp. e040965

Author(s):

Sandra Miriam Kawa ◽

Signe Benzon Larsen ◽

John Thomas Helgstrand ◽

Peter Iversen ◽

Klaus Brasso ◽

...

Keyword(s):

Prostate Cancer ◽

Systematic Review ◽

Data Extraction ◽

Specific Antigen ◽

Transrectal Ultrasound ◽

Population Based ◽

Free Text ◽

Medical Subject Headings ◽

Prognostic Information ◽

Prostate Biopsies

ObjectiveTo investigate the risk of prostate cancer-specific mortality (PCSM) following initial negative systematic transrectal ultrasound-guided (TRUS) prostate biopsies.DesignSystematic review.Data sourcesPubMed and Embase were searched using a string combination with keywords/Medical Subject Headings terms and free text in the search builder. Date of search was 13 April 2020.Study selectionStudies addressing PCSM following initial negative TRUS biopsies. Randomised controlled trials and population-based studies including men with initial negative TRUS biopsies reported in English from 1990 until present were included.Data extractionData extraction was done using a predefined form by two authors independently and compared with confirm data; risk of bias was assessed using the Newcastle–Ottawa Scale for cohort studies when applicable.ResultsFour eligible studies were identified. Outcomes were reported differently in the studies as both cumulative incidence and Kaplan-Meier estimates have been used. Regardless of the study differences, all studies reported low estimated incidence of PCSM of 1.8%–5.2% in men with negative TRUS biopsies during the following 10–20 years. Main limitation in all studies was limited follow-up.ConclusionOnly a few studies have investigated the risk of PCSM following initial negative biopsies and all studies included patients before the era of MRI of the prostate. However, the studies point to the fact that the risk of PCSM is low following initial negative TRUS biopsies, and that the level of prostate-specific antigen before biopsies holds prognostic information. This may be considered when advising patients about the need for further diagnostic evaluation.PROSPERO registration numberCRD42019134548.

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AR Splicing Variants and Resistance to AR Targeting Agents

Cancers ◽

10.3390/cancers13112563 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2563

Author(s):

Mayuko Kanayama ◽

Changxue Lu ◽

Jun Luo ◽

Emmanuel S. Antonarakis

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Splice Variants ◽

Treatment Options ◽

Predictive Biomarker ◽

Castration Resistant Prostate Cancer ◽

Treatment Benefit ◽

Novel Biomarkers ◽

The Many ◽

Preclinical And Clinical Studies

Over the past decade, advances in prostate cancer research have led to discovery and development of novel biomarkers and effective treatments. As treatment options diversify, it is critical to further develop and use optimal biomarkers for the purpose of maximizing treatment benefit and minimizing unwanted adverse effects. Because most treatments for prostate cancer target androgen receptor (AR) signaling, aberrations affecting this drug target are likely to emerge following the development of castration-resistant prostate cancer (CRPC), and it is conceivable that such aberrations may play a role in drug resistance. Among the many AR aberrations, we and others have been studying androgen receptor splice variants (AR-Vs), especially AR-V7, and have conducted preclinical and clinical studies to develop and validate the clinical utility of AR-V7 as a prognostic and potential predictive biomarker. In this review, we first describe mechanisms of AR-V generation, regulation and their functions from a molecular perspective. We then discuss AR-Vs from a clinical perspective, focusing on the significance of AR-Vs detected in different types of human specimens and AR-Vs as potential therapeutic targets.

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