Evaluation of cell-line-derived xenograft tumours as controls for immunohistochemical testing for ER and PR

Hasan, Tahrim; Carter, Beverley; Denic, Nash; Gai, Luis; Power, J; Voisey, Kim; Kao, Kenneth R.

doi:10.1136/jclinpath-2015-203066

Cited by 8 publications

(9 citation statements)

References 10 publications

(9 reference statements)

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“…MCF7 cells express high levels of ER,12 and as expected, MCF7 breast cancer CDX tumours consistently demonstrated strong expression of ER under standard preanalytical processing (10% NBF for 24 hours at RT). To assess the effects of variable FT on ER scoring, MCF7 CDX tumours were fixed for periods from 1 hour to 120 hours.…”

Section: Resultssupporting

confidence: 72%

“…Previously, we demonstrated that CDX tumours were suitable as homogenously expressing models that were reproducible, yet indistinguishable from tumour specimens submitted for biomarker reporting 12. Tumour cores were arranged on a microarray and blind-scored by all observers.…”

Section: Resultsmentioning

confidence: 99%

“…CDX tumours were obtained by growing cell lines in inmmunodeficient mice as described 12. Animal care (13-26-KK) and human investigation (KAO 15-281) clearances were obtained.…”

Section: Methodsmentioning

confidence: 99%

“…Previously, we demonstrated that cell-derived xenografted (CDX) tumours were indistinguishable from patient tumours for breast biomarker reporting, and most importantly for this study, do not display intertumoral heterogeneity 12. We examined the role of the length of time CDX tumours are placed in standard fixative on breast biomarker expression in human breast cancer cell-derived (CDX) tumours.…”

Section: Introductionmentioning

confidence: 92%

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Effect of fixation time on breast biomarker expression: a controlled study using cell line-derived xenografted (CDX) tumours

et al. 2017

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Section: Resultssupporting

confidence: 72%

Section: Resultsmentioning

confidence: 99%

“…CDX tumours were obtained by growing cell lines in inmmunodeficient mice as described 12. Animal care (13-26-KK) and human investigation (KAO 15-281) clearances were obtained.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

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Effect of fixation time on breast biomarker expression: a controlled study using cell line-derived xenografted (CDX) tumours

et al. 2017

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“…Several transgenic or knockout models for extra-uterine Müllerian/ovarian and for mammary carcinomas have been developed over the last 2 decades (see ( Pfefferle et al, 2013 , Hollern and Andrechek, 2014 , Hasan et al, 2015 ) for reviews). In some cases, specific pathways, including Her-2/neu in mammary epithelium, Pten in Müllerian epithelium, and others have been targeted while others have focused on Brca1 / 2 inactivation in tissues corresponding to those with an elevated cancer risk in human BRCA1 / 2 mutation carriers.…”

Section: Discussionmentioning

confidence: 99%

A Mouse Model That Reproduces the Developmental Pathways and Site Specificity of the Cancers Associated With the Human BRCA1 Mutation Carrier State

et al. 2015

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Predisposition to breast and extrauterine Müllerian carcinomas in BRCA1 mutation carriers is due to a combination of cell-autonomous consequences of BRCA1 inactivation on cell cycle homeostasis superimposed on cell-nonautonomous hormonal factors magnified by the effects of BRCA1 mutations on hormonal changes associated with the menstrual cycle. We used the Müllerian inhibiting substance type 2 receptor (Mis2r) promoter and a truncated form of the Follicle stimulating hormone receptor (Fshr) promoter to introduce conditional knockouts of Brca1 and p53 not only in mouse mammary and Müllerian epithelia, but also in organs that control the estrous cycle. Sixty percent of the double mutant mice developed invasive Müllerian and mammary carcinomas. Mice carrying heterozygous mutations in Brca1 and p53 also developed invasive tumors, albeit at a lesser (30%) rate, in which the wild type alleles were no longer present due to loss of heterozygosity. While mice carrying heterozygous mutations in both genes developed mammary tumors, none of the mice carrying only a heterozygous p53 mutation developed such tumors (P < 0.0001), attesting to a role for Brca1 mutations in tumor development. This mouse model is attractive to investigate cell-nonautonomous mechanisms associated with cancer predisposition in BRCA1 mutation carriers and to investigate the merit of chemo-preventive drugs targeting such mechanisms.

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Benchmarking to the Gold Standard: Hyaluronan‐Oxime Hydrogels Recapitulate Xenograft Models with In Vitro Breast Cancer Spheroid Culture

et al. 2019

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Many 3D in vitro models induce breast cancer spheroid formation; however, this alone does not recapitulate the complex in vivo phenotype. To effectively screen therapeutics, it is urgently needed to validate in vitro cancer spheroid models against the gold standard of xenografts. A new oxime‐crosslinked hyaluronan (HA) hydrogel is designed, manipulating gelation rate and mechanical properties to grow breast cancer spheroids in 3D. This HA‐oxime breast cancer model maintains the gene expression profile most similar to that of tumor xenografts based on a pan‐cancer gene expression profile (comprising 730 genes) of three different human breast cancer subtypes compared to Matrigel or conventional 2D culture. Differences in gene expression between breast cancer cultures in HA‐oxime versus Matrigel or 2D are confirmed for 12 canonical pathways by gene set variation analysis. Importantly, drug response is dependent on the culture method. Breast cancer cells respond better to the Rac inhibitor (EHT‐1864) and the PI3K inhibitor (AZD6482) when cultured in HA‐oxime versus Matrigel. This study demonstrates the superiority of an HA‐based hydrogel as a platform for in vitro breast cancer culture of both primary, patient‐derived cells and cell lines, and provides a hydrogel culture model that closely matches that in vivo.

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Evaluation of cell-line-derived xenograft tumours as controls for immunohistochemical testing for ER and PR

Cited by 8 publications

References 10 publications

Effect of fixation time on breast biomarker expression: a controlled study using cell line-derived xenografted (CDX) tumours

Effect of fixation time on breast biomarker expression: a controlled study using cell line-derived xenografted (CDX) tumours

A Mouse Model That Reproduces the Developmental Pathways and Site Specificity of the Cancers Associated With the Human BRCA1 Mutation Carrier State

Benchmarking to the Gold Standard: Hyaluronan‐Oxime Hydrogels Recapitulate Xenograft Models with In Vitro Breast Cancer Spheroid Culture

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