Non-Invasive Ultrasound Assessment of Endometrial Cancer Progression in Pax8-Directed Deletion of the Tumor Suppressors Arid1a and Pten in Mice

Rachel Vistein; Briana Winer; Stephanie Myers; Juliane Liberto; Shun Ishiyama; Xin Guo; Harumi Saeki; Tian-Li Wang; Ie-Ming Shih; Kathleen Gabrielson

doi:10.3791/64732

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Method Article

Non-Invasive Ultrasound Assessment of Endometrial Cancer Progression in Pax8-Directed Deletion of the Tumor Suppressors Arid1a and Pten in Mice

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DOI:

10.3791/64732

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February 17th, 2023

Rachel Vistein¹ , Briana Winer² , Stephanie Myers¹^,³ , Juliane Liberto⁴ , Shun Ishiyama¹^,⁵^,⁶ , Xin Guo¹ , Harumi Saeki⁷ , Tian-Li Wang⁴^,⁸ , Ie-Ming Shih²^,⁴^,⁸ , Kathleen Gabrielson¹^,⁴^,⁸

¹Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, ²Department of Obstetrics and Gynecology, Johns Hopkins University School of Medicine, ³Texas Tech University School of Veterinary Medicine, ⁴Department of Pathology, Johns Hopkins University School of Medicine, ⁵Department of Surgery, Johns Hopkins University School of Medicine, ⁶Department of Coloproctological Surgery, Juntendo University School of Medicine, ⁷Department of Human Pathology, Juntendo University School of Medicine, ⁸Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University

Summary

This protocol describes a method for monitoring the progression of morphological changes over time in the uterus in an inducible mouse model of endometrial cancer using ultrasound imaging with correlation to gross and histological changes.

Abstract

Uterine cancers can be studied in mice due to the ease of handling and genetic manipulation in these models. However, these studies are often limited to assessing pathology post-mortem in animals euthanized at multiple time points in different cohorts, which increases the number of mice needed for a study. Imaging mice in longitudinal studies can track the progression of disease in individual animals, reducing the number of mice needed. Advances in ultrasound technology have allowed for the detection of micrometer-level changes in tissues. Ultrasound has been used to study follicle maturation in ovaries and xenograft growth but has not been applied to morphological changes in the mouse uterus. This protocol examines the juxtaposition of pathology with in vivo imaging comparisons in an induced endometrial cancer mouse model. The features observed by ultrasound were consistent with the degree of change seen by gross pathology and histology. Ultrasound was found to be highly predictive of the observed pathology, supporting the incorporation of ultrasonography into longitudinal studies of uterine diseases such as cancer in mice.

Introduction

Mice remain one of the most important animal models for reproductive disorders¹^,²^,³. There are several genetically modified or induced rodent models of ovarian and uterine cancers. These studies typically rely on multiple cohorts euthanized at different time points to capture longitudinal trends in morphologic and pathologic changes. This prevents the ability to acquire continuous data on cancer development in an individual mouse. Additionally, without knowing the individual mouse disease progression state, intervention studies are based on predetermined time points and avera....