Detection of breast cancer lymph node metastases in frozen sections with a point-of-care low-cost microscope scanner

Holmström, O.; Linder, N.; Moilanen, H.; Suutala, A.; Nordling, S.; Stahls, A.; Lundin, M.; Diwan, V.; Lundin, J.

doi:10.1101/474106

Home/Archive/bioRxiv

bioRxiv · 10.1101/474106

Detection of breast cancer lymph node metastases in frozen sections with a point-of-care low-cost microscope scanner

Holmström, O.·Linder, N.·Moilanen, H.·Suutala, A.·Nordling, S.·Stahls, A.·Lundin, M.·Diwan, V.·Lundin, J.

View original source ↗Export metadata ↓

Abstract

BackgroundDetection of lymph node metastases is essential in breast cancer diagnostics and staging, affecting treatment and prognosis. Intraoperative microscopy analysis of sentinel lymph node frozen sections is standard for detection of axillary metastases, but requires access to a pathologist for sample analysis. Remote analysis of digitized samples is an alternative solution, but is limited by the requirement for high-end slide scanning equipment.\n\nObjectiveTo determine whether the image quality achievable with a low-cost, miniature digital microscope scanner is sufficient for detection of metastases in breast cancer lymph node frozen sections.\n\nMethodsLymph node frozen sections from 79 breast cancer patients were digitized using a prototype miniature microscope scanner and a high-end slide scanner. Images were independently reviewed by two pathologists and results compared between devices with conventional light microscopy analysis as ground truth.\n\nResultsDetection of metastases in the images acquired with the miniature scanner yielded an overall sensitivity of 91 % and specificity of 99 % and showed strong agreement when compared to light microscopy (k = 0.91). Strong agreement was also observed when results were compared to results from the high-end slide scanner (k = 0.94). A majority of discrepant cases were micrometastases and sections of which no anticytokeratin staining was available.\n\nConclusionAccuracy of detection of metastatic cells in breast cancer sentinel lymph node frozen sections by visual analysis of samples digitized using low-cost, point-of-care microscopy is comparable to analysis of digital samples scanned using a high-end, whole slide scanner. This technique could potentially provide a workflow for digital diagnostics in resource-limited settings, facilitate sample analysis at the point-of-care and reduce the need for trained experts on-site during surgical procedures.

Source connections

Published article ↗

Explore related subjects

pathology Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Holmström, O., Linder, N., Moilanen, H., Suutala, A., Nordling, S., Stahls, A., Lundin, M., Diwan, V., Lundin, J.. 2018-11-19. Detection of breast cancer lymph node metastases in frozen sections with a point-of-care low-cost microscope scanner. https://doi.org/10.1101/474106

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

NAE1-Dependent Protein Neddylation Preserves Endothelial Identity and Vascular Integrity

Background: Endothelial dysfunction is a central driver of cardiovascular and inflammatory diseases, yet the post-translational mechanisms that preserve endothelial homeostasis remain incompletely understood. Protein neddylation, the covalent conjugation of a ubiquitin-like modifier, regulates diverse cellular processes, yet its physiological role in the vascular endothelium remains unknown. This study investigated whether protein neddylation is required to preserve endothelial identity and vascular homeostasis. Methods: We generated tamoxifen-inducible endothelial-specific Nae1 knockout mice to inhibit neddylation and combined bulk RNA sequencing, single-cell and single-nucleus transcriptomics, quantitative proteomics, biochemical analyses, and gain- and loss-of-function approaches to define the role of endothelial neddylation in vascular homeostasis and inflammatory injury. Results: Endothelial-specific Nae1 deletion caused rapid mortality associated with vascular leakage, platelet accumulation, inflammation, and multi-organ injury. Multi-omics analyses demonstrated profound loss of endothelial identity, characterized by suppression of core endothelial programs and activation of inflammatory, procoagulant, and pyroptotic pathways. Single-cell analyses revealed progressive endothelial dysfunction culminating in depletion of the endothelial population and remodeling of the vascular niche. Mechanistically, endothelial neddylation deficiency activated gasdermin D (GSDMD)- and gasdermin E (GSDME)-dependent pyroptosis, whereas dual inhibition of GSDMD and GSDME markedly attenuated inflammatory transcriptomic remodeling, vascular injury, hepatocyte death, immune cell infiltration, and platelet accumulation. Translational analyses demonstrated reduced endothelial neddylation in experimental endotoxemia and decreased expression of neddylation pathway components in human atherosclerosis and COVID-19 datasets. Conversely, restoration of endothelial neddylation partially reversed inflammatory endothelial transcriptomic reprogramming in vivo. Conclusions: NAE1-dependent protein neddylation is an essential regulator of endothelial identity and vascular integrity. Loss of endothelial neddylation promotes gasdermin-dependent pyroptosis and thrombo-inflammatory vascular injury, whereas restoration of the neddylation pathway mitigates inflammatory endothelial dysfunction. These findings identify endothelial neddylation as a fundamental mechanism maintaining vascular homeostasis and a potential therapeutic target for cardiovascular and inflammatory diseases.

pathology↗

bioRxiv2018

Biological Potencial of Colletotrichum typhae H.C Greene mycoherbicide for Typha domingensis Pers

The anthropic interference in aquatic ecosystems, favors the disordered colonization of T. domingensis, damaging the production of hydroelectric power and river traffic. Thus, the objective of this study was to evaluate the potential of C. typhae as a mycoherbicide in the control of T. domingensis, in vitro and in greenhouse. 107 samples of symptomatic T. domingensis leaves were collected in flooded areas of rivers in Brazil, with identification and isolation of the collected fungal species. The concentration of inoculum was determined to evaluate the incidence and severity of the disease, the influence of temperature on mycelial growth and conidia germination, the effect of temperature and leaf wetness period on T. domingensis infection by C. typhae and the host range test. The growth of the colonies of C. typhae was higher at 25 to 30 {o}C, there was no interference of the photoperiod on germination of the spores, but the highest percentage of germination occurred at 17.39 {o}C. The influence of environmental conditions on infection of inoculated leaves of T. dominguensis indicated that at 15 {degrees}C and the period of leaf wetness of 48 hours promoted the highest incidence of the disease, as well as the severity for the same period of leaf wetness. The specificity test showed that C. typhae is specific and pathogenic to T. domingensis. Being this the first report of the occurrence of this pathogen in aquatic macrophytes of this species and in T. domingensis in Brazil.

pathology↗

bioRxiv2018

The α-tubulin of Laodelphax striatellus facilitates the passage of rice stripe virus (RSV) and enhances horizontal transmission

Rice stripe virus (RSV), causal agent of rice stripe disease, is transmitted by the small brown planthopper (SBPH, Laodelphax striatellus) in a persistent manner. The midgut and salivary glands of SBPH are the first and last barriers in viral circulation and transmission, respectively; however, the precise mechanisms used by RSV to cross these organs and re-inoculate rice have not been fully elucidated. We obtained full-length cDNA of L. striatellus -tubulin 2 (LsTUB) and found that RSV infection increased the level of LsTUB in vivo. Furthermore, LsTUB was shown to bind the RSV nonstructural protein 3 (NS3) in vitro. RNAi was used to reduce LsTUB expression, which caused a significant reduction in RSV titer, NS3 expression, RSV inoculation rates, and transmission to healthy plants. Electrical penetration graphs (EPG) showed that LsTUB knockdown by RNAi did not impact SBPH feeding; therefore, the reduction in RSV inoculation rate was likely caused by the decrease in RSV transmission. These findings suggest that LsTUB mediates the passage of RSV through midgut and salivary glands and leads to successful horizontal transmission.

pathology↗