Validation of an automated quantitative digital pathology approach for scoring TMEM: A prognostic biomarker for metastasis Journal Article


Authors: Entenberg, D.; Oktay, M. H.; D'Alfonso, T.; Ginter, P. S.; Robinson, B. D.; Xue, X.; Rohan, T. E.; Sparano, J. A.; Jones, J. G.; Condeelis, J. S.
Article Title: Validation of an automated quantitative digital pathology approach for scoring TMEM: A prognostic biomarker for metastasis
Abstract: Metastasis causes ~90% of breast cancer mortality. However, standard prognostic tests based mostly on proliferation genes do not measure metastatic potential. Tumor MicroEnvironment of Metastasis (TMEM), an immunohistochemical biomarker for doorways on blood vessels that support tumor cell dissemination is prognostic for metastatic outcome in breast cancer patients. Studies quantifying TMEM doorways have involved manual scoring by pathologists utilizing static digital microscopy: a labor-intensive process unsuitable for use in clinical practice. We report here a validation study evaluating a new quantitative digital pathology (QDP) tool (TMEM-DP) for identification and quantification of TMEM doorways that closely mimics pathologists’ workflow and reduces pathologists’ variability to levels suitable for use in a clinical setting. Blinded to outcome, QDP was applied to a nested case-control study consisting of 259 matched case-control pairs. Sixty subjects of these were manually scored by five pathologists, digitally recorded using whole slide imaging (WSI), and then used for algorithm development and optimization. Validation was performed on the remainder of the cohort. TMEM-DP shows excellent reproducibility and concordance and reduces pathologist time from ~60 min to ~5 min per case. Concordance between manual scoring and TMEM-DP was found to be >0.79. These results show that TMEM-DP is capable of accurately identifying and scoring TMEM doorways (also known as MetaSite score) equivalent to pathologists. © 2020 by the authors. Licensee MDPI, Basel, Switzerland. T.
Keywords: adult; controlled study; human tissue; human cell; major clinical study; case control study; reproducibility; metastasis; image analysis; cohort analysis; validation study; tumor marker; algorithm; quantitative analysis; scoring system; tumor microenvironment; digital pathology; prognostic; process optimization; cancer prognosis; human; article; prognostic assessment; tmem; tumor microenvironment of metastasis
Journal Title: Cancers
Volume: 12
Issue: 4
ISSN: 2072-6694
Publisher: MDPI  
Date Published: 2020-04-01
Start Page: 846
Language: English
DOI: 10.3390/cancers12040846
PROVIDER: scopus
PUBMED: 32244564
PMCID: PMC7226227
DOI/URL:
Notes: Article -- Source: Scopus
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