A novel histological examination with dynamic three‐dimensional reconstruction from multiple immunohistochemically stained sections of a <scp>PD</scp>‐L1‐positive colon cancer

Korehisa, Shotaro; Ikeda, Tetsuo; Okano, Shinji; Saeki, Hiroshi; Oki, Eiji; Oda, Yoshinao; Hashizume, Makoto; Maehara, Yoshihiko

doi:10.1111/his.13400

Cited by 14 publications

(19 citation statements)

References 10 publications

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“…To detect collagen fibers in colonic tissues, Masson trichrome staining was performed, according to the previously described method [22]. e sections were deparaffinized and rehydrated with xylene and 100, 95, and 70% ethanol.…”

Section: Masson Trichrome Stainingmentioning

confidence: 99%

Polydeoxyribonucleotide Exerts Therapeutic Effect by Increasing VEGF and Inhibiting Inflammatory Cytokines in Ischemic Colitis Rats

Kim

Jin

et al. 2020

BioMed Research International

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Ischemic colitis is resulted from an inadequate blood supply to a segment or entire colon. Polydeoxyribonucleotide (PDRN), extracted from salmon sperm, has been reported to exert anti-inflammatory and anti-ischemic effects through the adenosine A2A receptor (A2AR). We investigated whether PDRN possesses therapeutic effectiveness on ischemic colitis rats. Ischemic colitis was induced by selective devascularization. The skin temperature on the ischemic colitis-induced region was determined. To assess the colonic damage score and collagen deposition, colonic tissue sections were stained with hematoxylin and eosin (H&E), and Masson trichrome staining was performed. Western blot analysis for A2AR, vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6, Bax, Bcl-2, and extracellular signal-regulated kinase 1/2 (ERK1/2) was performed. Skin temperature was increased and mucosal damage and collagen deposition were observed in the affected colonic tissues in the ischemic colitis rats. Expressions of inflammatory cytokines (TNF-α, IL-1β, and IL-6) and inflammatory mediator (COX-2) were upregulated in the ischemic colitis rats. Apoptosis was increased by decreasing the ratio of Bcl-2 to Bax and by suppressing the phosphorylated form of ERK1/2 expression in the ischemic colitis rats. Treatment with PDRN alleviated mucosal damage reduced the expressions of inflammatory cytokines and COX-2 and inhibited apoptosis in the ischemic colitis rats. PDRN treatment more enhanced the expressions of A2AR and VEGF in the ischemic colitis rats. PDRN showed therapeutic effectiveness on ischemic colitis by increasing VEGF expression and inhibiting inflammatory cytokines and COX-2 through enhancing A2AR expression.

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Section: Masson Trichrome Stainingmentioning

confidence: 99%

Polydeoxyribonucleotide Exerts Therapeutic Effect by Increasing VEGF and Inhibiting Inflammatory Cytokines in Ischemic Colitis Rats

Kim

Jin

et al. 2020

BioMed Research International

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“…These advantages are crucial in the evaluation of PD-L1 expression. Compared to the 3D PD-L1 evaluation method developed by Korehisa et al [ 18 ], which was based on computer reconstruction of PD-L1 IHC image from serial thin sections, our method has the advantages of “true” 3D imaging and preserved tissue integrity after imaging for further pathological examinations. Compared to the method developed by Lee et al .…”

Section: Discussionmentioning

confidence: 99%

Computer-assisted three-dimensional quantitation of programmed death-ligand 1 in non-small cell lung cancer using tissue clearing technology

et al. 2022

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Immune checkpoint blockade therapy has revolutionized non-small cell lung cancer treatment. However, not all patients respond to this therapy. Assessing the tumor expression of immune checkpoint molecules, including programmed death-ligand 1 (PD-L1), is the current standard in predicting treatment response. However, the correlation between PD-L1 expression and anti-PD-1/PD-L1 treatment response is not perfect. This is partly caused by tumor heterogeneity and the common practice of assessing PD-L1 expression based on limited biopsy material. To overcome this problem, we developed a novel method that can make formalin-fixed, paraffin-embedded tissue translucent, allowing three-dimensional (3D) imaging. Our protocol can process tissues up to 150 μm in thickness, allowing anti-PD-L1 staining of the entire tissue and producing high resolution 3D images. Compared to a traditional 4 μm section, our 3D image provides 30 times more coverage of the specimen, assessing PD-L1 expression of approximately 10 times more cells. We further developed a computer-assisted PD-L1 quantitation method to analyze these images, and we found marked variation of PD-L1 expression in 3D. In 5 of 33 needle-biopsy-sized specimens (15.2%), the PD-L1 tumor proportion score (TPS) varied by greater than 10% at different depth levels. In 14 cases (42.4%), the TPS at different depth levels fell into different categories (< 1%, 1–49%, or ≥ 50%), which can potentially influence treatment decisions. Importantly, our technology permits recovery of the processed tissue for subsequent analysis, including histology examination, immunohistochemistry, and mutation analysis. In conclusion, our novel method has the potential to increase the accuracy of tumor PD-L1 expression assessment and enable precise deployment of cancer immunotherapy.

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“…Some studies 1 – 5 , 15 – 17 have provided valuable 3D information on microscopic morphology or gene expression of different types of tumors, by reconstruction of a part of the tumor tissues from 75 to 500 serial slices using different systems. The entire tumor is hard to reconstruct completely at high resolution owing to a number of difficulties, such as, size limitations of slide scanner and microtome, poor uniformity/quality of serial whole-organ sectioning and staining, the time-consuming nature of the procedure, computer constraints, and limited software processing capability.…”

Section: Discussionmentioning

confidence: 99%

“…However, they do not yield a satisfactory resolution to distinguish the tumor mass from normal tissue. Several studies have reported 3D models of tumor architecture based on reconstruction of light microscopic image sections 1 – 5 , which show promise in cancer research. However, ultrahigh-resolution 3D reconstruction of the entire bulk of a tumor is not yet to be achieved.…”

Section: Introductionmentioning

confidence: 99%

Three-dimensional reconstruction of laryngeal cancer with whole organ serial immunohistochemical sections

Tian

Qian

Zhang

et al. 2020

Sci Rep

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Three-dimensional (3D) image reconstruction of tumors based on serial histological sectioning is one of the most powerful methods for accurate high-resolution visualization of tumor structures. However, 3D histological reconstruction of whole tumor has not yet been achieved. We established a high-resolution 3D model of molecular marked whole laryngeal cancer by optimizing the currently available techniques. A series of 5,388 HE stained or immunohistochemically stained whole light microscopic images (200 ×) were acquired (15.61 TB).The data set of block-face images (96.2 GB) was also captured. Direct volume rendering of serial 6.25 × light microscopy images did not demonstrate the major characteristics of the laryngeal cancer as expected. Based on fusion of two datasets, the accurate boundary of laryngeal tumor bulk was visualized in an anatomically realistic context. In the regions of interest, micro tumor structure, budding, cell proliferation and tumor lymph vessels were well represented in 3D after segmentation, which highlighted the advantages of 3D reconstruction of light microscopy images. In conclusion, generating 3D digital histopathological images of a whole solid tumor based on current technology is feasible. However, data mining strategy should be developed for complete utilization of the large amount of data generated.

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A novel histological examination with dynamic three‐dimensional reconstruction from multiple immunohistochemically stained sections of a PD‐L1‐positive colon cancer

Abstract: We confirmed that PD-L1 was highly expressed in the invasive frontal region in 3D models of MSI-H colon cancer tissue. This method can be useful for accurately evaluating the localisation of immune checkpoint molecules.

Cited by 14 publications

References 10 publications

Polydeoxyribonucleotide Exerts Therapeutic Effect by Increasing VEGF and Inhibiting Inflammatory Cytokines in Ischemic Colitis Rats

Polydeoxyribonucleotide Exerts Therapeutic Effect by Increasing VEGF and Inhibiting Inflammatory Cytokines in Ischemic Colitis Rats

Computer-assisted three-dimensional quantitation of programmed death-ligand 1 in non-small cell lung cancer using tissue clearing technology

Three-dimensional reconstruction of laryngeal cancer with whole organ serial immunohistochemical sections

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