Evidence map›Paper›PMID 36309296›Full record

ArticleHuman pathology2022

Clonal relationships of adjacent Gleason pattern 3 and Gleason pattern 5 lesions in Gleason Scores 3+5=8 and 5+3=8.

Hasim Bakbak, Erolcan Sayar, Harsimar B Kaur, Daniela C Salles, Radhika A Patel, Jessica Hicks, Tamara L Lotan, Angelo M De Marzo, Roman Gulati, Jonathan I Epstein and 1 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Human pathology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
0.2field-weighted citation impact, top 48% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 1 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 1 country.

Hasim BakbakDivision of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, 98109, WA, USA.
Erolcan SayarDivision of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, 98109, WA, USA.
Harsimar B KaurDepartment of Oncology, The Johns Hopkins University School of Medicine, Baltimore, 21287, MD, USA.
Daniela C SallesDepartment of Oncology, The Johns Hopkins University School of Medicine, Baltimore, 21287, MD, USA.
Radhika A PatelDivision of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, 98109, WA, USA.
Jessica HicksDepartment of Pathology, The Johns Hopkins University School of Medicine, Baltimore, 21287, MD, USA.
Tamara L LotanDepartment of Pathology, The Johns Hopkins University School of Medicine, Baltimore, 21287, MD, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, 21287, MD, USA; Department of Urology, The Johns Hopkins University School of Medicine, Baltimore, 21287, MD, USA.
Angelo M De MarzoDepartment of Pathology, The Johns Hopkins University School of Medicine, Baltimore, 21287, MD, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, 21287, MD, USA; Department of Urology, The Johns Hopkins University School of Medicine, Baltimore, 21287, MD, USA.
Roman GulatiDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, 98109, WA, USA.
Jonathan I EpsteinDepartment of Pathology, The Johns Hopkins University School of Medicine, Baltimore, 21287, MD, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, 21287, MD, USA; Department of Urology, The Johns Hopkins University School of Medicine, Baltimore, 21287, MD, USA. Electronic address: jepstein@jhmi.edu.
Michael C HaffnerDivision of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, 98109, WA, USA; Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, 21287, MD, USA; Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, 98109, WA, USA; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, 98195, WA, USA. Electronic address: mhaffner@fredhutch.org.
Fred Hutch Cancer Center · USJohns Hopkins Medicine · USJohns Hopkins University · USUniversity of Washington · US

Funding

TRANSCRIPTOME AND PROTEOME STRATIFICATION OF PROSTATE ADENOCARCINOMA PHENOTYPESP50CA097186 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PETER S NELSON · 2002 to 2026
$58.1M
Statistical modeling to support population and translational cancer researchR50CA221836 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Roman Gulati · 2017 to 2026
$2.0M
NCI NIH HHS P50 CA097186NCI NIH HHS R50 CA221836
6 · The paper itself

Abstract

Genomic studies have demonstrated a high level of intra-tumoral heterogeneity in prostate cancer. There is strong evidence suggesting that individual tumor foci can arise as genetically distinct, clonally independent lesions. However, recent studies have also demonstrated that adjacent Gleason pattern (GP) 3 and GP4 lesions can originate from the same clone but follow divergent genetic and morphologic evolution. The clonal relationship of adjacent GP3 and GP5 lesions has thus far not been investigated. Here we analyzed a cohort of 14 cases-11 biopsy and 3 radical prostatectomy specimens-with a Gleason score of 3 + 5 = 8 or 5 + 3 = 8 present in the same biopsy or in a single dominant tumor nodule at radical prostatectomy. Clonal and subclonal relationships between GP3 and GP5 lesions were assessed using genetically validated immunohistochemical assays for ERG, PTEN, and P53. 9/14 (64%) cases showed ERG reactivity in both GP3 and GP5 lesions. Only 1/14 (7%) cases showed a discordant pattern with ERG staining present only in GP3. PTEN expression was lost in 2/14 (14%) cases with perfect concordance between GP5 and GP3. P53 nuclear reactivity was present in 1/14 (7%) case in both GP5 and GP3. This study provides first evidence that the majority of adjacent GP3 and GP5 lesions share driver alterations and are clonally related. In addition, we observed a lower-than-expected rate of PTEN loss in GP5 in the context of Gleason score 3 + 5 = 8 or 5 + 3 = 8 tumors.

Indexed as

Prostatic NeoplasmsTumor Suppressor Protein p53HumansMaleNeoplasm GradingProstateProstatectomyTumor Suppressor Protein p53ClonalityERGGleason pattern 5Gleason score 3+5P53Prostate cancerPTEN

Identifiers

PMID36309296
PMCPMC10542864
OpenAlexW4307570294

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.