Relationship between tumor grade and geometrical complexity in prostate cancer

Prostate cancer exhibits high mathematical complexity due to the disruption of tissue architecture. An important part of the diagnostic of prostate tumor samples is the histological evaluation of cellular and glandular organization. The Gleason grade and score, a commonly used prognostic indicator of patient outcome, is based on the match of glandular architectural patterns with standard patterns. Unfortunately, the subjective nature of visual grading leads to variations in scoring by different pathologists. We proposed the fractal dimension of the lumen and the Lempel-Zip complexity of the histopathological patterns as useful descriptors aiding pathologist to standardize histological classification and thus prognosis and therapy planning.

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Expression of NY-ESO-1 cancer testis antigen in prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e16544 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e16544-e16544 ◽

Cited By ~ 1

Author(s):

Rohit K. Jain ◽

Bo Xu ◽

Rutika Jitesh Mehta ◽

Elena Pop ◽

James Mohler ◽

...

Keyword(s):

Prostate Cancer ◽

Methylation Status ◽

Tumor Grade ◽

Staining Intensity ◽

Gleason Grade ◽

Limited Information ◽

Cytoplasmic Staining ◽

Poor Outcomes ◽

Epigenetic Modulation ◽

Cancer Testis

e16544 Background: Poor outcomes in castrate resistant prostate cancer (CRPC) patients is a growing concern urging the need for innovative treatments. Cancer testis antigens (CTAs) like NY-ESO-1 are aberrantly expressed in several cancers including prostate cancer (PC). Given its tumor-restricted expression and ability to elicit spontaneous cytotoxic & antibody-mediated immune responses, NY-ESO-1 shows promise as an immunotherapy target. With the expertise of RPCI in NY-ESO-1 targeted therapeutics and limited information on NY-ESO-1 expression in CRPC, we sought this study. Methods: Immunohistochemical expression of NY-ESO-1 was analyzed in a series of PC samples from 2 different institutions. Two TMAs consisted of triplicate cores from 37 patients with localized PC (with cores from cancerous areas & the normal tissue adjacent to it), and 36 mCRPC patients. We also included 17 mCRPC whole sections for analyses. Intensity and percentage of NY-ESO-1 staining were recorded. The intensity was characterized as low (0-1+) and high (2-3+). Results: The median age in this cohort was 62 years. NY-ESO-1 IHC was positive for cytoplasmic staining in 33 of 111 (26.4%) evaluable cases including 41% in localized PC, 22.6% in benign areas adjacent to tumor, and 35.5% in CRPC. 23 (18.4%) had 1+, 7 (5.6%) had 2+ and 3 (2.4%) had 3+ cytoplasmic staining intensity. No statistical difference was noted in cytoplasmic staining with tumor grade. Gleason grade 8 -10 tumors (33 of 103 [35.4%]) correlated with lower intensity staining (0-1+) pattern (p = 0.028). NY-ESO-1 expression did not correlate with age, race, disease free or overall survival in this cohort. Conclusions: Heterogeneous NY-ESO-1 expression in PC and other tumors is linked to DNA methylation status of its promoter and tumor cells. We noted NY-ESO-1 expression in a third of the patients with CRPC, making it a credible immunotherapeutic target. NY-ESO-1 expression has been shown to be induced and upregulated in cancer by treatment with demethylating agent. Thus targeting NY-ESO-1 in concert with epigenetic modulation maybe therapeutically meaningful in patients with CRPC. Additional efforts at validating NY-ESO-1 expression in CRPC with CLIA approved IHC and qPCR assays (Omniseq) are ongoing and will be reported.

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Computer extracted gland features from H&E predicts prostate cancer recurrence comparably to a genomic companion diagnostic test: a large multi-site study

npj Precision Oncology ◽

10.1038/s41698-021-00174-3 ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Patrick Leo ◽

Andrew Janowczyk ◽

Robin Elliott ◽

Nafiseh Janaki ◽

Kaustav Bera ◽

...

Keyword(s):

Prostate Cancer ◽

Diagnostic Tests ◽

Specific Antigen ◽

Cancer Recurrence ◽

Tumor Grade ◽

Gleason Grade ◽

Grade Group ◽

Companion Diagnostic ◽

Risk Patients ◽

Validation Set

AbstractExisting tools for post-radical prostatectomy (RP) prostate cancer biochemical recurrence (BCR) prognosis rely on human pathologist-derived parameters such as tumor grade, with the resulting inter-reviewer variability. Genomic companion diagnostic tests such as Decipher tend to be tissue destructive, expensive, and not routinely available in most centers. We present a tissue non-destructive method for automated BCR prognosis, termed "Histotyping", that employs computational image analysis of morphologic patterns of prostate tissue from a single, routinely acquired hematoxylin and eosin slide. Patients from two institutions (n = 214) were used to train Histotyping for identifying high-risk patients based on six features of glandular morphology extracted from RP specimens. Histotyping was validated for post-RP BCR prognosis on a separate set of n = 675 patients from five institutions and compared against Decipher on n = 167 patients. Histotyping was prognostic of BCR in the validation set (p < 0.001, univariable hazard ratio [HR] = 2.83, 95% confidence interval [CI]: 2.03–3.93, concordance index [c-index] = 0.68, median years-to-BCR: 1.7). Histotyping was also prognostic in clinically stratified subsets, such as patients with Gleason grade group 3 (HR = 4.09) and negative surgical margins (HR = 3.26). Histotyping was prognostic independent of grade group, margin status, pathological stage, and preoperative prostate-specific antigen (PSA) (multivariable p < 0.001, HR = 2.09, 95% CI: 1.40–3.10, n = 648). The combination of Histotyping, grade group, and preoperative PSA outperformed Decipher (c-index = 0.75 vs. 0.70, n = 167). These results suggest that a prognostic classifier for prostate cancer based on digital images could serve as an alternative or complement to molecular-based companion diagnostic tests.

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805: High-Level Cyclin D1 is Associated with High Gleason Grade and Predicts Worse Biochemical-Free Survival in Prostate Cancer

The Journal of Urology ◽

10.1016/s0022-5347(18)33041-6 ◽

2006 ◽

Vol 175 (4S) ◽

pp. 260-260

Author(s):

Rile Li ◽

Hong Dai ◽

Thomas M. Wheeler ◽

Anna Frolov ◽

Gustavo Ayala

Keyword(s):

Prostate Cancer ◽

Cyclin D1 ◽

Gleason Grade ◽

Free Survival ◽

High Level

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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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Overexpressed P75CUX1 promotes EMT in glioma infiltration by activating β-catenin

Cell Death and Disease ◽

10.1038/s41419-021-03424-1 ◽

2021 ◽

Vol 12 (2) ◽

Author(s):

Anqi Xu ◽

Xizhao Wang ◽

Jie Luo ◽

Mingfeng Zhou ◽

Renhui Yi ◽

...

Keyword(s):

Epithelial Mesenchymal Transition ◽

Tumor Grade ◽

Prognostic Indicator ◽

Migration And Invasion ◽

Poor Overall Survival ◽

Mesenchymal Transition ◽

Kaplan Meier ◽

Homeobox Protein

AbstractThe homeobox protein cut-like 1 (CUX1) comprises three isoforms and has been shown to be involved in the development of various types of malignancies. However, the expression and role of the CUX1 isoforms in glioma remain unclear. Herein, we first identified that P75CUX1 isoform exhibited consistent expression among three isoforms in glioma with specifically designed antibodies to identify all CUX1 isoforms. Moreover, a significantly higher expression of P75CUX1 was found in glioma compared with non-tumor brain (NB) tissues, analyzed with western blot and immunohistochemistry, and the expression level of P75CUX1 was positively associated with tumor grade. In addition, Kaplan–Meier survival analysis indicated that P75CUX1 could serve as an independent prognostic indicator to identify glioma patients with poor overall survival. Furthermore, CUX1 knockdown suppressed migration and invasion of glioma cells both in vitro and in vivo. Mechanistically, this study found that P75CUX1 regulated epithelial–mesenchymal transition (EMT) process mediated via β-catenin, and CUX1/β-catenin/EMT is a novel signaling cascade mediating the infiltration of glioma. Besides, CUX1 was verified to promote the progression of glioma via multiple other signaling pathways, such as Hippo and PI3K/AKT. In conclusion, we suggested that P75CUX1 could serve as a potential prognostic indicator as well as a novel treatment target in malignant glioma.

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Clinical Stage, Prostate-Specific Antigen and Gleason Grade to Predict Extracapsular Disease or Nodal Metastasis in Men with Newly Diagnosed, Previously Untreated Prostate Cancer

European Urology ◽

10.1159/000480824 ◽

1997 ◽

Vol 32 (3) ◽

pp. 273-279 ◽

Cited By ~ 11

Author(s):

Paolo Puppo ◽

Massimo Perachino

Keyword(s):

Prostate Cancer ◽

Prostate Specific Antigen ◽

Clinical Stage ◽

Specific Antigen ◽

Nodal Metastasis ◽

Gleason Grade ◽

Newly Diagnosed

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Interchangeability of light and virtual microscopy for histopathological evaluation of prostate cancer

Scientific Reports ◽

10.1038/s41598-021-82911-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Renata Zelic ◽

Francesca Giunchi ◽

Luca Lianas ◽

Cecilia Mascia ◽

Gianluigi Zanetti ◽

...

Keyword(s):

Prostate Cancer ◽

Virtual Microscopy ◽

Observer Agreement ◽

Gleason Grade ◽

Gleason Grading ◽

Gleason Pattern ◽

Inter Observer Variability ◽

Histopathological Evaluation ◽

Good Repeatability ◽

Repeatability And Reproducibility

AbstractVirtual microscopy (VM) holds promise to reduce subjectivity as well as intra- and inter-observer variability for the histopathological evaluation of prostate cancer. We evaluated (i) the repeatability (intra-observer agreement) and reproducibility (inter-observer agreement) of the 2014 Gleason grading system and other selected features using standard light microscopy (LM) and an internally developed VM system, and (ii) the interchangeability of LM and VM. Two uro-pathologists reviewed 413 cores from 60 Swedish men diagnosed with non-metastatic prostate cancer 1998–2014. Reviewer 1 performed two reviews using both LM and VM. Reviewer 2 performed one review using both methods. The intra- and inter-observer agreement within and between LM and VM were assessed using Cohen’s kappa and Bland and Altman’s limits of agreement. We found good repeatability and reproducibility for both LM and VM, as well as interchangeability between LM and VM, for primary and secondary Gleason pattern, Gleason Grade Groups, poorly formed glands, cribriform pattern and comedonecrosis but not for the percentage of Gleason pattern 4. Our findings confirm the non-inferiority of VM compared to LM. The repeatability and reproducibility of percentage of Gleason pattern 4 was poor regardless of method used warranting further investigation and improvement before it is used in clinical practice.

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Prostate Cancer: Population-Based Survival Rates in Central Italy

Tumori Journal ◽

10.1177/030089169508100202 ◽

1995 ◽

Vol 81 (2) ◽

pp. 81-85 ◽

Cited By ~ 3

Author(s):

Emanuele Crocetti ◽

Eva Buiatti ◽

Andrea Amorosi

Keyword(s):

Prostate Cancer ◽

Central Italy ◽

Survival Rates ◽

Relative Survival ◽

Tumor Grade ◽

Population Based ◽

Prognostic Effect ◽

Disease Extension ◽

The One ◽

Histological Verification

Aims To evaluate survival in prostate cancer patients in the Province of Florence where the Tuscany Cancer Registry is active. Methods The survival of 777 patients with prostate cancer diagnosed in the period 1985-87 was evaluated. The observed and relative survival rates 1, 3 and 5 years after diagnosis were computed. Also the prognostic effect of age, disease extension, tumor grade, histological verification, place of residence and year of diagnosis were evaluated using univariate and multivariate analysis. Results The observed survival was 73.4% 1 year, 42.5% 3 years and 29.2% 5 years after diagnosis. The relative survival was respectively 78.7%, 53.0% and 43.0%. Significant independent risks were evident when the disease was extended out of the prostate, for patients older than 80 years, for high grade tumors and for patients without histological verification. Conclusion The 5-year relative survival rate in the province of Florence is similar to those from other European Registries and the Latina Registry, but much lower than the one reported by the SEER program in the US. Data on histological verification percentage, availability of information on disease extension, and tumor grade are discussed as indicators of the quality of the diagnostic approach in comparison with other registries.

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