Evidence map›Paper›PMID 38532196›Full record

ArticleVirchows Archiv : an international journal of pathology2025

Digital counting of tissue cells for molecular analysis: the QuANTUM pipeline.

Vincenzo L'Imperio, Giorgio Cazzaniga, Mauro Mannino, Davide Seminati, Francesco Mascadri, Joranda Ceku, Gabriele Casati, Francesca Bono, Catarina Eloy, Elena Guerini Rocco and 4 more

Open access · hybridAbstract read
In one paragraph

Article in Virchows Archiv : an international journal of pathology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed, 11 citations in OpenAlex.

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  10. Deep learning algorithm on H&E whole slide images to characterizeComputational and structural biotechnology journal · 2024
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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

14 authors at 5 institutions in 2 countries.

Vincenzo L'ImperioDepartment of Medicine and Surgery, Pathology, IRCCS Fondazione San Gerardo Dei Tintori, University of Milano-Bicocca, Milan, Italy. vincenzo.limperio@unimib.it.ORCID http://orcid.org/0000-0002-9284-2998
Giorgio CazzanigaDepartment of Medicine and Surgery, Pathology, IRCCS Fondazione San Gerardo Dei Tintori, University of Milano-Bicocca, Milan, Italy.ORCID http://orcid.org/0000-0001-5373-0611
Mauro ManninoDepartment of Medicine and Surgery, Pathology, IRCCS Fondazione San Gerardo Dei Tintori, University of Milano-Bicocca, Milan, Italy.
Davide SeminatiDepartment of Medicine and Surgery, Pathology, IRCCS Fondazione San Gerardo Dei Tintori, University of Milano-Bicocca, Milan, Italy.ORCID http://orcid.org/0000-0002-2166-301X
Francesco MascadriDepartment of Medicine and Surgery, Pathology, IRCCS Fondazione San Gerardo Dei Tintori, University of Milano-Bicocca, Milan, Italy.
Joranda CekuDepartment of Medicine and Surgery, Pathology, IRCCS Fondazione San Gerardo Dei Tintori, University of Milano-Bicocca, Milan, Italy.
Gabriele CasatiDepartment of Medicine and Surgery, Pathology, IRCCS Fondazione San Gerardo Dei Tintori, University of Milano-Bicocca, Milan, Italy.
Francesca BonoDepartment of Medicine and Surgery, Pathology, IRCCS Fondazione San Gerardo Dei Tintori, University of Milano-Bicocca, Milan, Italy.
Catarina EloyPathology Laboratory, Institute of Molecular Pathology and Immunology of University of Porto (IPATIMUP), Porto, Portugal.
Elena Guerini RoccoDivision of Pathology, European Institute of Oncology IRCCS, Milan, Italy.
Chiara FrascarelliDivision of Pathology, European Institute of Oncology IRCCS, Milan, Italy.
Matteo FassanSurgical Pathology and Cytopathology Unit, Department of Medicine, DIMED, University of Padua, Padua, Italy.
Umberto MalapelleDepartment of Public Health, University of Naples Federico II, Naples, Italy.
Fabio PagniDepartment of Medicine and Surgery, Pathology, IRCCS Fondazione San Gerardo Dei Tintori, University of Milano-Bicocca, Milan, Italy.ORCID http://orcid.org/0000-0001-9625-1637
University of Milano-Bicocca · ITUniversity of Milan · ITUniversidade do Porto · PTUniversity of Naples Federico II · ITUniversity of Padua · IT

Funding

Ministero dell'Istruzione, dell'Università e della Ricerca art. 1Ministero dell'Istruzione, dell'Università e della Ricerca commi 314 - 337)Ministero dell'Istruzione, dell'Università e della Ricerca Dipartimenti di Eccellenza 2023-2027 (l. 232/2016
6 · The paper itself

Abstract

The estimation of tumor cellular fraction (TCF) is a crucial step in predictive molecular pathology, representing an entry adequacy criterion also in the next-generation sequencing (NGS) era. However, heterogeneity of quantification practices and inter-pathologist variability hamper the robustness of its evaluation, stressing the need for more reliable results. Here, 121 routine histological samples from non-small cell lung cancer (NSCLC) cases with complete NGS profiling were used to evaluate TCF interobserver variability among three different pathologists (pTCF), developing a computational tool (cTCF) and assessing its reliability vs ground truth (GT) tumor cellularity and potential impact on the final molecular results. Inter-pathologist reproducibility was fair to good, with overall Wk ranging between 0.46 and 0.83 (avg. 0.59). The obtained cTCF was comparable to the GT (p = 0.129, 0.502, and 0.130 for surgical, biopsies, and cell block, respectively) and demonstrated good reliability if elaborated by different pathologists (Wk = 0.9). Overall cTCF was lower as compared to pTCF (30 ± 10 vs 52 ± 19, p < 0.001), with more cases < 20% (17, 14%, p = 0.690), but none containing < 100 cells for the algorithm. Similarities were noted between tumor area estimation and pTCF (36 ± 29, p < 0.001), partly explaining variability in the human assessment of tumor cellularity. Finally, the cTCF allowed a reduction of the copy number variations (CNVs) called (27 vs 29, - 6.9%) with an increase of effective CNVs detection (13 vs 7, + 85.7%), some with potential clinical impact previously undetected with pTCF. An automated computational pipeline (Qupath Analysis of Nuclei from Tumor to Uniform Molecular tests, QuANTUM) has been created and is freely available as a QuPath extension. The computational method used in this study has the potential to improve efficacy and reliability of TCF estimation in NSCLC, with demonstrated impact on the final molecular results.

Indexed as

Carcinoma, Non-Small-Cell LungLung NeoplasmsPathology, MolecularBiomarkers, TumorHigh-Throughput Nucleotide SequencingHumansObserver VariationReproducibility of ResultsBiomarkers, TumorComputational pathologyMolecular pathologyNGSNon-small cell lung cancerTumor cellular fraction

Identifiers

PMID38532196
PMCPMC11876257
OpenAlexW4393184333

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.