Evidence map›Paper›PMID 29138507›Full record

ArticleScientific reports2017

Systems pathology by multiplexed immunohistochemistry and whole-slide digital image analysis.

Sami Blom, Lassi Paavolainen, Dmitrii Bychkov, Riku Turkki, Petra Mäki-Teeri, Annabrita Hemmes, Katja Välimäki, Johan Lundin, Olli Kallioniemi, Teijo Pellinen

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed
22.1field-weighted citation impact, top 1% 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

98 citing papers in PubMed, 160 citations in OpenAlex.

  1. PD-L1Haematologica · 2018
    Trial
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Multiplexed Immunophenotyping of Lymphoma Tissue Samples.Methods in molecular biology (Clifton, N.J.) · 2025
    Article
  15. AneRBC dataset: a benchmark dataset for computer-aided anemia diagnosis using RBC images.Database : the journal of biological databases and curation · 2024
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

38 more citing papers are in PubMed but not listed here.

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

10 authors at 1 institution in 2 countries.

Sami BlomInstitute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland.ORCID 0000-0002-1878-8911
Lassi PaavolainenInstitute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland.
Dmitrii BychkovInstitute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland.
Riku TurkkiInstitute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland.ORCID 0000-0002-8690-6983
Petra Mäki-TeeriInstitute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland.
Annabrita HemmesInstitute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland.
Katja VälimäkiInstitute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland.
Johan LundinInstitute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland.
Olli KallioniemiInstitute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland.ORCID 0000-0002-3231-0332
Teijo PellinenInstitute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland. teijo.pellinen@helsinki.fi.
University of Helsinki · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The paradigm of molecular histopathology is shifting from a single-marker immunohistochemistry towards multiplexed detection of markers to better understand the complex pathological processes. However, there are no systems allowing multiplexed IHC (mIHC) with high-resolution whole-slide tissue imaging and analysis, yet providing feasible throughput for routine use. We present an mIHC platform combining fluorescent and chromogenic staining with automated whole-slide imaging and integrated whole-slide image analysis, enabling simultaneous detection of six protein markers and nuclei, and automatic quantification and classification of hundreds of thousands of cells in situ in formalin-fixed paraffin-embedded tissues. In the first proof-of-concept, we detected immune cells at cell-level resolution (n = 128,894 cells) in human prostate cancer, and analysed T cell subpopulations in different tumour compartments (epithelium vs. stroma). In the second proof-of-concept, we demonstrated an automatic classification of epithelial cell populations (n = 83,558) and glands (benign vs. cancer) in prostate cancer with simultaneous analysis of androgen receptor (AR) and alpha-methylacyl-CoA (AMACR) expression at cell-level resolution. We conclude that the open-source combination of 8-plex mIHC detection, whole-slide image acquisition and analysis provides a robust tool allowing quantitative, spatially resolved whole-slide tissue cytometry directly in formalin-fixed human tumour tissues for improved characterization of histology and the tumour microenvironment.

Indexed as

Biomarkers, TumorCell SeparationHumansImage Processing, Computer-AssistedImmunohistochemistryMaleProstatic NeoplasmsReceptors, AndrogenTumor MicroenvironmentAR protein, humanBiomarkers, TumorReceptors, Androgen

Identifiers

PMID29138507
PMCPMC5686230
OpenAlexW2768059176

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.