| 1. |
- Mucchiano, Gerd, et al.
(författare)
-
Apolipoprotein A-1-derived amyloid in atherosclerotic plaques of the human aorta
- 2001
-
Ingår i: Journal of Pathology. - 0022-3417 .- 1096-9896. ; 193:2, s. 270-275
-
Tidskriftsartikel (refereegranskat)abstract
- Previous studies have shown that the amyloid localized to the aortic intima may be a biochemical entity different from other forms of localized amyloid. The amyloid fibril protein in one patient studied consisted of an N-terminal fragment of apolipoprotein A-1 (apo A-1). Since this patient was later shown to carry a missense mutation in the apo A-1 gene, leading to a deletion at position 107 of the mature protein, the question remained whether wild-type apo A-1 is amyloidogenic. In autopsy specimens from the thoracic aorta from 69 individuals, intimal atherosclerotic plaque-related amyloid was present in 11 cases (16%) and amyloid outside plaques in 37 cases (54%). The immunoreactivity of amyloid localized to the aortic intima was evaluated with the aid of antisera against N-terminal segments of apo A-1. The amyloid in association with atherosclerotic plaques was positively labelled by immunohistochemistry. The amyloid fibril protein from one patient, previously shown not to carry any mutation in the apo A-1 gene, was purified and shown by amino acid sequence analysis to be of apo A-1 nature. The result shows that wild-type apo A-1 is amyloidogenic and gives rise to a common localized form of amyloid associated with atherosclerosis.
|
|
| 2. |
- Wester, Kenneth, et al.
(författare)
-
Cultured human fibroblasts in agarose gel as a multi-functional control for immunohistochemistry : Standardization Of Ki67 (MIB1) assessment in routinely processed urinary bladder carcinoma tissue
- 2000
-
Ingår i: Journal of Pathology. - 0022-3417 .- 1096-9896. ; 190:4, s. 503-11
-
Tidskriftsartikel (refereegranskat)abstract
- Immunohistochemistry (IHC) in clinical practice is hampered by lack of standardization and by subjectivity in interpretation and quantitation. This study aimed to develop a control system for IHC in routinely fixed and histoprocessed tissues. Such a system should be easy to handle in clinical practice and should reflect variations in fixation time, section thickness, section storage conditions, and staining protocols. In addition, in image analysis quantitation of immunostained tissues, when using classifiers computed on IHC-control images, the control system should be very stable. Cultured human fibroblasts were suspended in agarose, transferred into a length of tubing and stored at 4 degrees C. Three pieces of the cellgel control were separately fixed, histoprocessed, and paraffin-embedded as external controls. One piece was prepared together with each of 18 bladder carcinoma biopsies as internal controls. Slides with sections from the biopsy and all types of cellgel controls were stored at different temperatures and then stained using three different IHC protocols. The fibroblasts were homogeneously distributed in the agarose gel. Variation in section thickness did not influence immunostaining as evaluated by the MIB1 labelling index (MIB1 LI). The external controls decreased notably in MIB1 LI with increased fixation time. This was not seen in the 18 internal controls that were each fixed with a fresh biopsy. However, section storage and immunostaining conditions influenced the MIB1 expression equally in all control types and to a similar degree to the biopsies. Furthermore, colour-based image analysis quantitation of MIB1 LI in biopsies proved stable and independent of the control type used to compute the classifier.
|
|
| 3. |
- Abels, Esther, et al.
(författare)
-
Computational pathology definitions, best practices, and recommendations for regulatory guidance: a white paper from the Digital Pathology Association
- 2019
-
Ingår i: Journal of Pathology. - : WILEY. - 0022-3417 .- 1096-9896. ; 249:3, s. 286-294
-
Forskningsöversikt (refereegranskat)abstract
- In this white paper, experts from the Digital Pathology Association (DPA) define terminology and concepts in the emerging field of computational pathology, with a focus on its application to histology images analyzed together with their associated patient data to extract information. This review offers a historical perspective and describes the potential clinical benefits from research and applications in this field, as well as significant obstacles to adoption. Best practices for implementing computational pathology workflows are presented. These include infrastructure considerations, acquisition of training data, quality assessments, as well as regulatory, ethical, and cyber-security concerns. Recommendations are provided for regulators, vendors, and computational pathology practitioners in order to facilitate progress in the field. (c) 2019 The Authors. The Journal of Pathology published by John Wiley amp; Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Azevedo, M, et al.
(författare)
-
Infection by Helicobacter pylori expressing the BabA adhesin is influenced by the secretor phenotype
- 2008
-
Ingår i: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 215:3, s. 308-316
-
Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori (Hp) infects half the world's population and causes diverse gastric lesions, from gastritis to gastric cancer. Our aim was to evaluate the significance of secretor and Lewis status in infection and in vitro adherence by Hp expressing BabA adhesin. We enrolled 304 Hp-infected individuals from Northern Portugal. Gastric biopsies, blood and saliva were collected. Polymerase chain reaction (PCR) and immunofluorescence were used to detect BabA+ Hp in gastric biopsies. In vitro adherence by a BabA expressing Hp strain to gastric biopsies was performed. Secretor status was identified by Ulex, a lectin that recognizes secretor-dependent glycan structures in saliva and in gastric mucosa, and by Lewis(a/b) antibodies, and indirectly by identification of an inactivating mutation in the FUT2 gene (G428A). BabA status of infecting Hp was associated with CagA and VacAs1 (p < 0.05), intercellular localization of Hp (p < 0.01) and the presence of intestinal metaplasia (p < 0.05) and degenerative alterations (p < 0.005) in the biopsies. BabA was associated (p < 0.05) with Ulex staining of gastric biopsies and, although not significantly, to absence of homozygosity for FUT2 G428A inactivating polymorphism. In vitro Hp adherence was higher in cases wild-type or heterozygous for FUT2 G428A mutation (p < 0.0001), cases staining for Ulex (p < 0.0001) and a(-)b+ and a(-)b(-) secretor phenotypes (p < 0.001). In conclusion, BabA+ Hp infection/adhesion is secretor-dependent and associated with the severity of gastric lesions.
|
|
| 8. |
- Backman, Max, et al.
(författare)
-
Infiltration of NK and plasma cells is associated with a distinct immune subset in non‐small cell lung cancer
- 2021
-
Ingår i: Journal of Pathology. - : John Wiley & Sons. - 0022-3417 .- 1096-9896. ; 255:3, s. 243-256
-
Tidskriftsartikel (refereegranskat)abstract
- Immune cells of the tumor microenvironment are central but erratic targets for immunotherapy. The aim of this study was to characterize novel patterns of immune cell infiltration in non-small cell lung cancer (NSCLC) in relation to its molecular and clinicopathologic characteristics. Lymphocytes (CD3+, CD4+, CD8+, CD20+, FOXP3+, CD45RO+), macrophages (CD163+), plasma cells (CD138+), NK cells (NKp46+), PD1+, and PD-L1+ were annotated on a tissue microarray including 357 NSCLC cases. Somatic mutations were analyzed by targeted sequencing for 82 genes and a tumor mutational load score was estimated. Transcriptomic immune patterns were established in 197 patients based on RNA sequencing data. The immune cell infiltration was variable and showed only poor association with specific mutations. The previously defined immune phenotypic patterns, desert, inflamed, and immune excluded, comprised 30, 13, and 57% of cases, respectively. Notably, mRNA immune activation and high estimated tumor mutational load were unique only for the inflamed pattern. However, in the unsupervised cluster analysis, including all immune cell markers, these conceptual patterns were only weakly reproduced. Instead, four immune classes were identified: (1) high immune cell infiltration, (2) high immune cell infiltration with abundance of CD20+ B cells, (3) low immune cell infiltration, and (4) a phenotype with an imprint of plasma cells and NK cells. This latter class was linked to better survival despite exhibiting low expression of immune response-related genes (e.g. CXCL9, GZMB, INFG, CTLA4). This compartment-specific immune cell analysis in the context of the molecular and clinical background of NSCLC reveals two previously unrecognized immune classes. A refined immune classification, including traits of the humoral and innate immune response, is important to define the immunogenic potency of NSCLC in the era of immunotherapy. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
|
|
| 9. |
- Bekkhus, Tove, et al.
(författare)
-
Automated detection of vascular remodeling in human tumor draining lymph nodes by the deep learning tool HEV-finder
- 2022
-
Ingår i: Journal of Pathology. - : John Wiley & Sons. - 0022-3417 .- 1096-9896. ; 258:1, s. 4-11
-
Tidskriftsartikel (refereegranskat)abstract
- Vascular remodeling is common in human cancer and has potential as future biomarkers for prediction of disease progression and tumor immunity status. It can also affect metastatic sites, including the tumor-draining lymph nodes (TDLNs). Dilation of the high endothelial venules (HEVs) within TDLNs has been observed in several types of cancer. We recently demonstrated that it is a premetastatic effect that can be linked to tumor invasiveness in breast cancer. Manual visual assessment of changes in vascular morphology is a tedious and difficult task, limiting high-throughput analysis. Here we present a fully automated approach for detection and classification of HEV dilation. By using 12,524 manually classified HEVs, we trained a deep-learning model and created a graphical user interface for visualization of the results. The tool, named the HEV-finder, selectively analyses HEV dilation in specific regions of the lymph nodes. We evaluated the HEV-finder's ability to detect and classify HEV dilation in different types of breast cancer compared to manual annotations. Our results constitute a successful example of large-scale, fully automated, and user-independent, image-based quantitative assessment of vascular remodeling in human pathology and lay the ground for future exploration of HEV dilation in TDLNs as a biomarker.
|
|
| 10. |
- Bekkhus, T., et al.
(författare)
-
Automated detection of vascular remodeling in tumor-draining lymph nodes by the deep-learning tool HEV-finder
- 2022
-
Ingår i: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 258:1, s. 4-11
-
Tidskriftsartikel (refereegranskat)abstract
- Vascular remodeling is common in human cancer and has potential as future biomarkers for prediction of disease progression and tumor immunity status. It can also affect metastatic sites, including the tumor-draining lymph nodes (TDLNs). Dilation of the high endothelial venules (HEVs) within TDLNs has been observed in several types of cancer. We recently demonstrated that it is a premetastatic effect that can be linked to tumor invasiveness in breast cancer. Manual visual assessment of changes in vascular morphology is a tedious and difficult task, limiting high-throughput analysis. Here we present a fully automated approach for detection and classification of HEV dilation. By using 12,524 manually classified HEVs, we trained a deep-learning model and created a graphical user interface for visualization of the results. The tool, named the HEV-finder, selectively analyses HEV dilation in specific regions of the lymph nodes. We evaluated the HEV-finder's ability to detect and classify HEV dilation in different types of breast cancer compared to manual annotations. Our results constitute a successful example of large-scale, fully automated, and user-independent, image-based quantitative assessment of vascular remodeling in human pathology and lay the ground for future exploration of HEV dilation in TDLNs as a biomarker. (c) 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
|
|
