Establishment and characterization of organoids from a patient with adenomyoepithelioma of the breast

Abstract

Adenomyoepithelioma (AME) of the breast is a rare tumor that is composed of proliferating epithelial and myoepithelial cells. The pathogenesis of AME remains unclear, and no breast cancer cells have been identified in such tumor tissues. In this study, we established patient-derived breast cancer organoids from the surgical tumor samples of an elderly Chinese woman with an AME of the breast. Our findings confirmed the successful establishment of organoids from an AME of the breast of this patient. A short tandem repeat analysis revealed that the DNA signature of the AME of the breast organoids matched the DNA signature of the original tumor specimen. Moreover, diameter assay confirmed that the organoids from the breast AME showed sensitivity to paclitaxel and doxorubicin treatments, which was similar to, but lesser than that of primary culture cells. In conclusion, we established an efficient 3-dimensional breast cancer organoid culture platform from an AME of the breast. This platform can be effectively used for exploring clinicopathological and genomic characteristics of AME of the breast to identify possible treatments and increase awareness about this disease entity.

GelMA, Click-Chemistry Gelatin and Bioprinted Polyethylene Glycol-Based Hydrogels as 3D Ex Vivo Drug Testing Platforms for Patient-Derived Breast Cancer Organoids

“…The incorporation of ECM-based matrices surrounding PDOs is likely to drastically change drug responses. In a study by Luo et al, for example, PDOs were made out of a case of adenomyoepithelioma of the breast reliant on self-assembled matrix-free spheroids [ 75 ]. While the diameter of the organoids successfully grew from 20 to 80 µm from 1 to 7 days of culture and decreased with increased drug concentrations, the effect of doxorubicin and paclitaxel were similar at similar doses (between 500 and 1000 nM) [ 75 ].…”

“…In a study by Luo et al, for example, PDOs were made out of a case of adenomyoepithelioma of the breast reliant on self-assembled matrix-free spheroids [ 75 ]. While the diameter of the organoids successfully grew from 20 to 80 µm from 1 to 7 days of culture and decreased with increased drug concentrations, the effect of doxorubicin and paclitaxel were similar at similar doses (between 500 and 1000 nM) [ 75 ]. This is unlikely to recapitulate the physiological scenario, where ECM proteins would have reduced drug diffusion [ 8 ] and modulated apoptotic effects [ 62 ] and not line with clinical response for these drugs.…”

Cancer organoids: A platform in basic and translational research

“…Dekkers et al described a protocol for long-term culture of normal human breast and breast cancer organoids from clinical samples 15 and a diverse biobank of normal and breast cancer PDOs with a focus on triple-negative breast cancer (TNBC) has been compiled. 39 In addition, organoids have been used to study rare cancers, such as adenomyoepithelioma, 40 papillary carcinomas, 41 Paget's disease, 42 and TNBC with malignant pleural effusion, 43 and genes mimicking neoplasia have been knocked out by CRISPR/Cas9 in organoids for transplant into mice. 44 Furthermore, patient-specific drug sensitivity may be evaluated in vitro organoids to guide treatment.…”

Tumor Organoids as a Research Tool: How to Exploit Them

“…A particular niche where traditional in vitro models are often missing and where tumor organoids can really stand out is rare cancer types [ 100 , 101 ]. For example, they can be used to elucidate disease mechanisms of rare subtypes of prostate cancer [ 91 ] and can benefit patients with cholangiocarcinoma [ 102 ], appendiceal cancer [ 103 , 104 ], adenomyoepithelioma [ 105 ] and pancreatic neuroendocrine cancer [ 106 ].…”