Evidence map›Paper›PMID 33586037›Full record

ArticleMedical oncology (Northwood, London, England)2021

De novo neuroendocrine transdifferentiation in primary prostate cancer-a phenotype associated with advanced clinico-pathologic features and aggressive outcome.

Eman Abdulfatah, Zachery R Reichert, Matthew S Davenport, Arul M Chinnaiyan, Vipulkumar Dadhania, Xiaoming Wang, Rahul Mannan, Lakshmi P Kunju, Brent K Hollenbeck, Jeffrey S Montgomery and 9 more

Abstract read
PubMed Publisher
In one paragraph

Article in Medical oncology (Northwood, London, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

14 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Article
  3. Framework for the Pathology Workup of Metastatic Castration-Resistant Prostate Cancer Biopsies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
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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

19 authors at 2 institutions in 2 countries.

Eman AbdulfatahDepartment of Pathology, University of Michigan Medical School, 2800 Plymouth Road, Building 35, Ann Arbor, MI, USA.
Zachery R ReichertDepartment of Hematology/Oncology, University of Michigan, Ann Arbor, MI, USA.
Matthew S DavenportDepartment of Urology, University of Michigan Medical School, Ann Arbor, MI, USA.
Arul M ChinnaiyanDepartment of Pathology, University of Michigan Medical School, 2800 Plymouth Road, Building 35, Ann Arbor, MI, USA.
Vipulkumar DadhaniaDepartment of Pathology, University of Michigan Medical School, 2800 Plymouth Road, Building 35, Ann Arbor, MI, USA.
Xiaoming WangDepartment of Pathology, University of Michigan Medical School, 2800 Plymouth Road, Building 35, Ann Arbor, MI, USA.
Rahul MannanDepartment of Pathology, University of Michigan Medical School, 2800 Plymouth Road, Building 35, Ann Arbor, MI, USA.
Lakshmi P KunjuDepartment of Pathology, University of Michigan Medical School, 2800 Plymouth Road, Building 35, Ann Arbor, MI, USA.
Brent K HollenbeckDepartment of Urology, University of Michigan Medical School, Ann Arbor, MI, USA.
Jeffrey S MontgomeryDepartment of Urology, University of Michigan Medical School, Ann Arbor, MI, USA.
Samuel D KaffenbergerDepartment of Urology, University of Michigan Medical School, Ann Arbor, MI, USA.
Todd M MorganDepartment of Urology, University of Michigan Medical School, Ann Arbor, MI, USA.
Ajjai S AlvaDepartment of Hematology/Oncology, University of Michigan, Ann Arbor, MI, USA.
Ganesh S PalapattuDepartment of Urology, University of Michigan Medical School, Ann Arbor, MI, USA.
Ulka N VaishampayanDepartment of Hematology/Oncology, University of Michigan, Ann Arbor, MI, USA.
Joshi J AlumkalDepartment of Hematology/Oncology, University of Michigan, Ann Arbor, MI, USA.
Daniel E SprattDepartment of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA.
Aaron M UdagerDepartment of Pathology, University of Michigan Medical School, 2800 Plymouth Road, Building 35, Ann Arbor, MI, USA.
Rohit MehraDepartment of Pathology, University of Michigan Medical School, 2800 Plymouth Road, Building 35, Ann Arbor, MI, USA. mrohit@med.umich.edu.ORCID http://orcid.org/0000-0002-6955-8884
University of Michigan · USHoward Hughes Medical Institute · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Neuroendocrine transdifferentiation of high-grade prostate cancer (PCA-NT) comprises a morphologic and immunophenotypic transition from conventional adenocarcinoma towards high-grade neuroendocrine/small cell carcinoma. This phenomenon is frequently observed post androgen deprivation and/or radiotherapy, but de novo instances are increasingly recognized. Herein, we report a series of de novo PCA-NT focusing on characteristic morphologic, immunophenotypic and clinical features. Treatment naïve PCA-NT were identified. IHC for PSA, NKX3.1, Chromogranin, Synaptophysin, Cyclin D1, RB and Ki67 were performed. Radiology, treatment and follow-up data were reviewed. Sixteen patients were included. Apart from focal areas of high-grade prostate cancer with acinar features (reminiscent of Grade Group 5 disease), extensive areas with sheets of cells with deep amphophilic/basophilic cytoplasm, enlarged, hyperchromatic nuclei with granular chromatin and inconspicuous to prominent nucleoli with high mitotic activity were identified. Immunohistochemistry showed patchy NKX3.1, patchy PSA, variable Synaptophysin and Chromogranin; RB and CyclinD1 showed loss of expression. Ki67 showed high proliferative index, in most cases. Adverse radiologic findings and metastases were documented in most cases. Two patients died of disease. De novo PCA-NT exhibits high-grade nuclei, high mitotic activity, reduced PSA expression with high Ki67 and functional inactivation of RB1 pathway, suggesting transition from androgen-driven to proliferation-driven phenotype. Most cases presented at advanced stage with adverse radiological findings, metastasis at time of diagnosis, and high mortality. In light of their prognostic and therapeutic implications, pathologists may need to maintain a sensitive threshold for performing immunostains-in particular, Ki67 and CyclinD1-when presented with such cases in their day to day clinical practice.

Indexed as

Cell TransdifferentiationAgedAged, 80 and overBiomarkers, TumorHumansMaleMiddle AgedNeuroendocrine CellsPrognosisProstatic NeoplasmsBiomarkers, TumorHigh-gradeNeuroendocrineProstate cancerTransdifferentiation

Identifiers

PMID33586037
OpenAlexW3132478449

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.