Evidence mapPaperPMID 42417209Full record

ArticleThe journal of pathology. Clinical research2026

Mechanosensitive TRPV4 immunohistochemistry improves deep learning-based classification of ductal carcinoma in situ beyond H&E morphology.

Janghyun Yoo, Raghav Karthikeyan, Kashi Kamat, Christopher Chan, Shabnam Samankan, Elham Arbzadeh, Arnold Schwartz, Patricia S Latham, Inhee Chung

Abstract readMulticenter Study
In one paragraph

Article in The journal of pathology. Clinical research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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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

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Janghyun Yoo *Department of Physics and Astronomy, College of Natural Sciences, Seoul National University, Seoul, South Korea.
Raghav Karthikeyan *Department of Anatomy and Cell Biology, School of Medicine and Health Sciences, George Washington University, Washington, DC, USA.
Kashi KamatDepartment of Anatomy and Cell Biology, School of Medicine and Health Sciences, George Washington University, Washington, DC, USA.
Christopher ChanDepartment of Anatomy and Cell Biology, School of Medicine and Health Sciences, George Washington University, Washington, DC, USA.
Shabnam SamankanDepartment of Pathology, School of Medicine and Health Sciences, George Washington University, Washington, DC, USA.
Elham ArbzadehDepartment of Pathology, School of Medicine and Health Sciences, George Washington University, Washington, DC, USA.
Arnold SchwartzDepartment of Pathology, School of Medicine and Health Sciences, George Washington University, Washington, DC, USA.
Patricia S LathamDepartment of Pathology, School of Medicine and Health Sciences, George Washington University, Washington, DC, USA.
Inhee ChungDepartment of Anatomy and Cell Biology, School of Medicine and Health Sciences, George Washington University, Washington, DC, USA.ORCID https://orcid.org/0000-0002-2312-6357

Funding

Elsa U. Pardee FoundationGW Cancer Center Katzen Research ProgramNCI NIH HHSTechnology Maturation Award from the George Washington University Technology Commercialization Office
6 · The paper itself

Abstract

Ductal carcinoma in situ (DCIS) spans a biologic continuum from atypical ductal hyperplasia (ADH) to high-grade lesions with variable risk of progression to invasive ductal carcinoma (IDC), yet morphologic assessment by hematoxylin and eosin (H&E) remains diagnostically limited, particularly at the benign versus ADH/low-grade DCIS boundary. TRPV4, a mechanosensitive ion channel with pathology-dependent subcellular localization in DCIS, offers a biologically motivated immunohistochemical (IHC) marker that may refine classification beyond routine H&E assessment. We tested whether deep learning models trained on TRPV4 IHC outperform H&E-based models across the DCIS progression spectrum. We assembled a multi-institutional cohort of H&E and TRPV4 IHC whole-slide images from 108 patients, comprising an internal development cohort (n = 69), an external test cohort (n = 39), yielding 24,248 annotated tiles. Histopathological tiles from annotated regions were grouped into four ordered classes: normal/benign, ADH/low-grade DCIS, high-grade DCIS, and IDC. Xception and EfficientNet-B0 convolutional neural networks were trained with patient-level three-fold cross-validation on the development cohort and evaluated as ensembles on the external test cohort. On external patient-level testing, H&E ensembles achieved macro-F1 values of 0.43-0.44 and macro-AUC values of 0.73-0.80, whereas TRPV4 IHC ensembles improved performance to macro-F1 values of 0.68-0.72 and macro-AUC values of 0.91-0.92, corresponding to a 54.5-67.4% relative improvement in patient-level macro-F1. Patient-level per-class analyses showed the largest AUC gains with TRPV4 IHC versus H&E for ADH/low-grade DCIS (0.94-0.95 versus 0.61-0.70) and IDC (0.77-0.85 versus 0.61-0.69). Per-class analyses showed the largest gains with TRPV4 IHC versus H&E for ADH/low-grade DCIS (AUC, 0.83-0.84 versus 0.70-0.81) and IDC (AUC, 0.74-0.79 versus 0.65-0.66). These findings support TRPV4 IHC as a mechanistically grounded complement to H&E that improves patient-level discrimination across the DCIS progression spectrum, with the strongest gains for ADH/low-grade DCIS and IDC, in a pilot multi-institutional setting.

Indexed as

Biomarkers, TumorBreast NeoplasmsCarcinoma, Ductal, BreastCarcinoma, Intraductal, NoninfiltratingDeep LearningTRPV Cation ChannelsFemaleHumansImmunohistochemistryBiomarkers, TumorTRPV4 protein, humanTRPV Cation Channelsbreast pathologyconvolutional neural networksdeep learningdigital pathologyductal carcinoma in situexternal validationhistopathologic classificationimmunohistochemistryTRPV4whole‐slide imaging

Identifiers

PMID42417209
PMCPMC13343292

What Socratic holds

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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 Socratic graph.