Keratoacanthoma Pathobiology in Mouse Models

Recently we described skin tumors driven by skin-specific expression of Zmiz1 and here we define keratoacanthoma pathobiology in this mouse model. Similar to human keratoacanthoma development, we were able to segregate murine keratoacanthomas into three developmental phases: growth, maturation, and...

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Main Authors:	Gibson-Corley, Katherine N., Rogers, Laura M., Goeken, Adam, Dupuy, Adam J., Meyerholz, David K.
Format:	Online
Language:	English
Published:	2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190131/

id	pubmed-4190131
recordtype	oai_dc
spelling	pubmed-41901312015-05-23 Keratoacanthoma Pathobiology in Mouse Models Gibson-Corley, Katherine N. Rogers, Laura M. Goeken, Adam Dupuy, Adam J. Meyerholz, David K. Article Recently we described skin tumors driven by skin-specific expression of Zmiz1 and here we define keratoacanthoma pathobiology in this mouse model. Similar to human keratoacanthoma development, we were able to segregate murine keratoacanthomas into three developmental phases: growth, maturation, and regression. These tumors had areas with cellular atypia, high mitotic rate, and minor local invasion in the growth phase, but with development they transitioned to maturation and regression phases with evidence of resolution. The early aggressive appearance could easily be misdiagnosed as a malignant change if the natural pathobiology was not well-defined in the model. To corroborate these findings in the Zmiz1 model, we examined squamous skin tumors from another tumor study in aging mice, and these tumors followed a similar biological progression. Lastly, we were able to evaluate the utility of the model to assess immune cell infiltration (F4/80, B220 Granzyme B, CD3 cells, arginase-1) in the regression phase; however, because inflammation was present at all phases of development, a more comprehensive approach will be needed in future investigations. Our study of keratoacanthomas in selected murine models suggests that these squamous tumors can appear histologically aggressive during early development, but with time will enter a regression phase indicating a benign biology. Importantly, studies of squamous skin tumor models should be cautious in tumor diagnosis as the early growth distinction between malignant versus benign based solely on histopathology may not be easily discerned without longitudinal studies to confirm the tumor pathobiology. 2014-05-23 /pmc/articles/PMC4190131/ /pubmed/25309748 http://dx.doi.org/10.3390/diseases2020106 Text en © 2014 by the authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Gibson-Corley, Katherine N. Rogers, Laura M. Goeken, Adam Dupuy, Adam J. Meyerholz, David K.
spellingShingle	Gibson-Corley, Katherine N. Rogers, Laura M. Goeken, Adam Dupuy, Adam J. Meyerholz, David K. Keratoacanthoma Pathobiology in Mouse Models
author_facet	Gibson-Corley, Katherine N. Rogers, Laura M. Goeken, Adam Dupuy, Adam J. Meyerholz, David K.
author_sort	Gibson-Corley, Katherine N.
title	Keratoacanthoma Pathobiology in Mouse Models
title_short	Keratoacanthoma Pathobiology in Mouse Models
title_full	Keratoacanthoma Pathobiology in Mouse Models
title_fullStr	Keratoacanthoma Pathobiology in Mouse Models
title_full_unstemmed	Keratoacanthoma Pathobiology in Mouse Models
title_sort	keratoacanthoma pathobiology in mouse models
description	Recently we described skin tumors driven by skin-specific expression of Zmiz1 and here we define keratoacanthoma pathobiology in this mouse model. Similar to human keratoacanthoma development, we were able to segregate murine keratoacanthomas into three developmental phases: growth, maturation, and regression. These tumors had areas with cellular atypia, high mitotic rate, and minor local invasion in the growth phase, but with development they transitioned to maturation and regression phases with evidence of resolution. The early aggressive appearance could easily be misdiagnosed as a malignant change if the natural pathobiology was not well-defined in the model. To corroborate these findings in the Zmiz1 model, we examined squamous skin tumors from another tumor study in aging mice, and these tumors followed a similar biological progression. Lastly, we were able to evaluate the utility of the model to assess immune cell infiltration (F4/80, B220 Granzyme B, CD3 cells, arginase-1) in the regression phase; however, because inflammation was present at all phases of development, a more comprehensive approach will be needed in future investigations. Our study of keratoacanthomas in selected murine models suggests that these squamous tumors can appear histologically aggressive during early development, but with time will enter a regression phase indicating a benign biology. Importantly, studies of squamous skin tumor models should be cautious in tumor diagnosis as the early growth distinction between malignant versus benign based solely on histopathology may not be easily discerned without longitudinal studies to confirm the tumor pathobiology.
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190131/
_version_	1613142142207655936

Keratoacanthoma Pathobiology in Mouse Models

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