title: Quantitative assessment of pancreatic cancer precursor lesions in IHC-stained tissue with a tissue image analysis platform.
abstract: Tissue image analysis (tIA) is emerging as a powerful tool for quantifying biomarker expression and distribution in complex diseases and tissues. Pancreatic ductal adenocarcinoma (PDAC) develops in a highly complex and heterogeneous tissue environment and, generally, has a very poor prognosis. Early detection of PDAC is confounded by limited knowledge of the pre-neoplastic disease stages and limited methods to quantitatively assess disease heterogeneity. We sought to develop a tIA approach to assess the most common PDAC precursor lesions, pancreatic intraepithelial neoplasia (PanIN), in tissues from KrasLSL-G12D/+; Trp53LSL-R172H/+; Pdx-Cre (KPC) mice, a validated model of PDAC development. tIA profiling of training regions of PanIN and tumor microenvironment (TME) cells was utilized to guide identification of PanIN/TME tissue compartment stratification criteria. A custom CellMap algorithm implementing these criteria was applied to whole-slide images of KPC mice pancreata sections to quantify p53 and Ki-67 biomarker staining in each tissue compartment as a proof-of-concept for the algorithm platform. The algorithm robustly identified a higher percentage of p53-positive cells in PanIN lesions relative to the TME, whereas no difference was observed for Ki-67. Ki-67 expression was also quantified in a human pancreatic tissue sample available to demonstrate the translatability of the CellMap algorithm to human samples. Together, our data demonstrated the utility of CellMap to enable objective and quantitative assessments, across entire tissue sections, of PDAC precursor lesions in preclinical and clinical models of this disease to support efforts leading to novel insights into disease progression, diagnostic markers, and potential therapeutic targets.
authors: Flagship Biosciences Inc., Westminster, CO, USA.
authors: Famke
authors: F
authors: Aeffner
authors: Flagship Biosciences Inc., Westminster, CO, USA.
authors: Nathan T
authors: NT
authors: Martin
authors: Flagship Biosciences Inc., Westminster, CO, USA.
authors: Mirza
authors: M
authors: Peljto
authors: Flagship Biosciences Inc., Westminster, CO, USA.
authors: Joshua C
authors: JC
authors: Black
authors: Flagship Biosciences Inc., Westminster, CO, USA.
authors: Justin K
authors: JK
authors: Major
authors: Centre for Cancer and Inflammation, Barts Cancer Institute, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK.
authors: Maryam
authors: M
authors: Jangani
authors: Gilead Sciences, Seattle, WA, USA.
authors: Michael O
authors: MO
authors: Ports
authors: Flagship Biosciences Inc., Westminster, CO, USA.
authors: Joseph S
authors: JS
authors: Krueger
authors: Flagship Biosciences Inc., Westminster, CO, USA.
authors: G David
authors: GD
authors: Young
mesh_terms: D065311:Adenocarcinoma in Situ / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D000465:Algorithms; D000818:Animals; D057205:Automation, Laboratory; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D055088:Early Detection of Cancer / Q000379:methods; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D010179:Pancreas / Q000378:metabolism / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D012984:Software; D013047:Specific Pathogen-Free Organisms; D014015:Tissue Banks; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014463:Ultrasonography
chemical_list: D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53