The value of GATA6 immunohistochemistry and computer-assisted diagnosis to predict clinical outcome in advanced pancreatic cancer

Abstract Combination chemotherapy, either modified FOLFIRINOX (mFFX) or gemcitabine–nabpaclitaxel, are used in the treatment of most patients with advanced pancreatic ductal adenocarcinoma (PDAC), yet robust biomarkers of outcome are currently lacking to guide regimen selection. Here, we tested GATA...

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Autores principales:	Kai Duan, Gun-Ho Jang, Robert C. Grant, Julie M. Wilson, Faiyaz Notta, Grainne M. O’Kane, Jennifer J. Knox, Steven Gallinger, Sandra Fischer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/73ccc66b28ee408c885e22f743c92bee
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spelling	oai:doaj.org-article:73ccc66b28ee408c885e22f743c92bee2021-12-02T17:55:13ZThe value of GATA6 immunohistochemistry and computer-assisted diagnosis to predict clinical outcome in advanced pancreatic cancer10.1038/s41598-021-94544-32045-2322https://doaj.org/article/73ccc66b28ee408c885e22f743c92bee2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94544-3https://doaj.org/toc/2045-2322Abstract Combination chemotherapy, either modified FOLFIRINOX (mFFX) or gemcitabine–nabpaclitaxel, are used in the treatment of most patients with advanced pancreatic ductal adenocarcinoma (PDAC), yet robust biomarkers of outcome are currently lacking to guide regimen selection. Here, we tested GATA6 immunohistochemistry (IHC) as a putative biomarker in advanced PDAC. GATA6 is a transcription factor in normal pancreas development. Two pathologists, blinded to clinical and molecular data, independently assessed GATA6 IHC in biopsy specimens of 130 patients with advanced PDAC, in 2 distinct phases (without and with computer assistance using the open source software QuPath). Low GATA6 IHC expression was associated with shorter overall survival [median OS 6.2 months for patients with GATA6 low tumors vs. 11.5 months for patients with GATA6 high tumors, HR 1.66 (95% CI 1.15–2.40), P = 0.007]. Progression appears to be higher in GATA6-low tumors compared to GATA6-high tumors in patients treated with mFFX (P = 0.024) but not in patients treated with gemcitabine regimens. GATA6 IHC expression was significantly associated with molecular subtypes (P = 0.0003). Digital assistance markedly improved interrater concordance (Cohen’s kappa scores of 0.32 vs. 0.95). Our results provide strong evidence that GATA6 IHC can be used as a single biomarker in the clinic to predict clinical outcome in advanced PDAC, warranting further investigation in prospective clinical trials. These results provide the basis for an improved classification of PDAC and future biomarker design using digital pathology workflow.Kai DuanGun-Ho JangRobert C. GrantJulie M. WilsonFaiyaz NottaGrainne M. O’KaneJennifer J. KnoxSteven GallingerSandra FischerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kai Duan Gun-Ho Jang Robert C. Grant Julie M. Wilson Faiyaz Notta Grainne M. O’Kane Jennifer J. Knox Steven Gallinger Sandra Fischer The value of GATA6 immunohistochemistry and computer-assisted diagnosis to predict clinical outcome in advanced pancreatic cancer
description	Abstract Combination chemotherapy, either modified FOLFIRINOX (mFFX) or gemcitabine–nabpaclitaxel, are used in the treatment of most patients with advanced pancreatic ductal adenocarcinoma (PDAC), yet robust biomarkers of outcome are currently lacking to guide regimen selection. Here, we tested GATA6 immunohistochemistry (IHC) as a putative biomarker in advanced PDAC. GATA6 is a transcription factor in normal pancreas development. Two pathologists, blinded to clinical and molecular data, independently assessed GATA6 IHC in biopsy specimens of 130 patients with advanced PDAC, in 2 distinct phases (without and with computer assistance using the open source software QuPath). Low GATA6 IHC expression was associated with shorter overall survival [median OS 6.2 months for patients with GATA6 low tumors vs. 11.5 months for patients with GATA6 high tumors, HR 1.66 (95% CI 1.15–2.40), P = 0.007]. Progression appears to be higher in GATA6-low tumors compared to GATA6-high tumors in patients treated with mFFX (P = 0.024) but not in patients treated with gemcitabine regimens. GATA6 IHC expression was significantly associated with molecular subtypes (P = 0.0003). Digital assistance markedly improved interrater concordance (Cohen’s kappa scores of 0.32 vs. 0.95). Our results provide strong evidence that GATA6 IHC can be used as a single biomarker in the clinic to predict clinical outcome in advanced PDAC, warranting further investigation in prospective clinical trials. These results provide the basis for an improved classification of PDAC and future biomarker design using digital pathology workflow.
format	article
author	Kai Duan Gun-Ho Jang Robert C. Grant Julie M. Wilson Faiyaz Notta Grainne M. O’Kane Jennifer J. Knox Steven Gallinger Sandra Fischer
author_facet	Kai Duan Gun-Ho Jang Robert C. Grant Julie M. Wilson Faiyaz Notta Grainne M. O’Kane Jennifer J. Knox Steven Gallinger Sandra Fischer
author_sort	Kai Duan
title	The value of GATA6 immunohistochemistry and computer-assisted diagnosis to predict clinical outcome in advanced pancreatic cancer
title_short	The value of GATA6 immunohistochemistry and computer-assisted diagnosis to predict clinical outcome in advanced pancreatic cancer
title_full	The value of GATA6 immunohistochemistry and computer-assisted diagnosis to predict clinical outcome in advanced pancreatic cancer
title_fullStr	The value of GATA6 immunohistochemistry and computer-assisted diagnosis to predict clinical outcome in advanced pancreatic cancer
title_full_unstemmed	The value of GATA6 immunohistochemistry and computer-assisted diagnosis to predict clinical outcome in advanced pancreatic cancer
title_sort	value of gata6 immunohistochemistry and computer-assisted diagnosis to predict clinical outcome in advanced pancreatic cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/73ccc66b28ee408c885e22f743c92bee
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The value of GATA6 immunohistochemistry and computer-assisted diagnosis to predict clinical outcome in advanced pancreatic cancer

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