Part I: Basic Considerations and Recommendations for Preparation, Measurement and Interpretation

Haroske, G.; Giroud, Françoise; Reith, Albrecht; Böcking, Alfred

doi:10.1155/1998/390837

Cited by 111 publications

(76 citation statements)

References 29 publications

(32 reference statements)

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“…For each case, one 40-Am section of paraffinembedded tissue obtained from the same block as that assessed by immunohistochemistry was used to prepare nuclei as described (40,41). The Fairfield DNA Ploidy System (Fairfield Imaging, Ltd.) was used for image processing, analysis, and classification as previously described (40).…”

Section: Methodsmentioning

confidence: 99%

DNA Replication Licensing Factors and Aurora Kinases are Linked to Aneuploidy and Clinical Outcome in Epithelial Ovarian Carcinoma

Kulkarni

Loddo

Leo³

et al. 2007

Clinical Cancer Research

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Purpose: DNA replication licensing factors and Aurora kinases play critical roles in maintaining genomic integrity. We used multiparameter analyses of these cell cycle regulatory proteins to investigate their role in the progression of epithelial ovarian carcinoma (EOC). Experimental Design: In a cohort of 143 patients, we linked the protein expression profiles of the proliferation marker Ki67, the replication licensing factors Mcm2 and geminin, and the Aurora A and B kinases to tumor DNA ploidy status and clinical outcome. Results: Ki67, Mcm2, geminin, and Aurora A and B are significantly associated with tumor grade and ploidy status (P < 0.0001). Aurora A and its substrate H3S10ph are also significantly associated with Federation of International Obstetricians and Gynecologists tumor stage (P = 0.006 and P = 0.002, respectively). Aurora A and tumor ploidy status are predictive of disease-free survival in this cohort [hazard ratio (HR), 1.29; 95% confidence intervals (95% CI), 1.06-1.58, P = 0.01and HR, 1.80 (1.05-3.08), P = 0.03, respectively], with Aurora A of particular prognostic importance in early stage disease [HR, 1.72 (1.19-2.48), P = 0.004 for disease-free survival and HR, 1.81 (1.14-2.87), P = 0.01for overall survival]. Conclusions: Our data show that Ki67, Mcm2, geminin and Aurora A and B can be used as an adjunct to conventional prognostic indicators and as an aid to develop a tumor progression model for EOC. Dysregulation of Aurora A seems to be an early event in EOC with a key role in tumor progression. In view of present drug development programs for specific Aurora kinase inhibitors, our findings have important implications for the use of Aurora A as a biomarker and as a potential therapeutic target.

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Section: Methodsmentioning

confidence: 99%

DNA Replication Licensing Factors and Aurora Kinases are Linked to Aneuploidy and Clinical Outcome in Epithelial Ovarian Carcinoma

Kulkarni

Loddo

Leo³

et al. 2007

Clinical Cancer Research

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“…Strikingly, the proportions of abnormally sized nuclei in wt and p53-null cultures rose to 30 and 44%, respectively. As the enlarged nuclei of transdifferentiating cells could be attributed to cell spreading, we investigated whether increased nuclear area was associated with amplified DNA content, by measuring integrated optical density (IOD), the cytometric equivalent of DNA content (Haroske et al, 1998).…”

Section: Nuclearity Of Transdifferentiating Cells Is Determined By Abmentioning

confidence: 99%

“…We measured nuclear area and DNA content in acinar cultures in situ by image analysis and static cytometry (Haroske et al, 1998). Images of Feulgen-stained nuclei were captured with the Kontron Electronik Prog/Res/3012 system and a Zeiss Axioskop microscope.…”

Section: Measurement Of Nuclear Area and Integrated Optical Densitymentioning

confidence: 99%

p53 deficiency exacerbates pleiotropic mitotic defects, changes in nuclearity and polyploidy in transdifferentiating pancreatic acinar cells

Sphyris

Harrison

2005

Oncogene

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In a primary culture model for pancreatic acinar-ductal transdifferentiation, cells exhibited increased proliferation, changes in nuclearity and polyploidy. We identify the 'nucleus to centrosome' ratio of the progenitor cell, the dissemination of centrosomes at spindle poles and cytokinesis failure as critical determinants of mitosis outcome and centrosome inheritance. Abortive cytokinesis of mononuclear cells contributes to the binuclear cell pool, whereas enclosure of entire mitotic formations, within a single nuclear envelope, perpetuates polyploidization. Binuclear cell nuclei combine their genomes on a single metaphase plate, doubling descendant ploidy. Moreover, B42% of binuclear and tetraploid cells assemble aberrant spindles with up to 8 centrosomes/poles. These phenotypes were exacerbated in p53-deficient cultures exhibiting increased S-phase entry, giant nuclei, multinucleation, multipolar mitoses and centrosome hyperamplification. The tendency of p53-proficient cells to spontaneously evade the tetraploidy checkpoint degenerates to uncontrolled polyploid progression in p53-deficient cultures, explaining why p53 abrogation alone rapidly descends to aneuploidy in this system. We detected constitutively nuclear mdm2, which may circumvent endogenous cellcycle checkpoints, and pronounced accumulation of p21 and p27 in multinuclear cells and giant nuclei, consistent with roles in polyploidization. This in vitro model may recapitulate the processes underlying genomic instability in pancreatic tumours in vivo, and attests to the existence of a p53-dependent polyploidy checkpoint acting to limit the degree of polyploidization.

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“…As widely used in image cytometry studies, 56,57 lymphocytes were chosen for internal controls in this study.…”

Section: Controlsmentioning

confidence: 99%

Whole slide image cytometry: a novel method to detect abnormal DNA content in Barrett's esophagus

Wang

McManus

Arthur

et al. 2015

Laboratory Investigation

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Barrett's esophagus (BE) is a precursor of esophageal adenocarcinoma (EAC). Both low-grade dysplasia (LGD) and highgrade dysplasia (HGD) are associated with an increased risk of progression to EAC. However, histological interpretation and grading of dysplasia (particularly LGD) is subjective and poorly reproducible. This study has combined whole slide imaging with DNA image cytometry to provide a novel method for the detection of abnormal DNA content through image analysis of tissue sections. A total of 20 cases were evaluated, including 8 negative for dysplasia (NFD), 6 LGD, and 6 HGD. Feulgenstained esophageal sections were scanned in their entirety. Barrett's mucosa was interactively chosen for automatic nuclei segmentation where irrelevant cell types were ignored. The combined DNA content histogram for all nuclei within selected image regions was then obtained. In addition, three histogram measurements were computed, including xER-5C, 2cDI, and DNA-MG. Visual evaluation suggested the shape of DNA content histograms from NFD, LGD, and HGD cases exhibiting identifiable differences. The histogram measurements, xER-5C, 2cDI, and DNA-MG, were shown to be effective in differentiating metaplastic from dysplastic cases with statistical significance. Moreover, they also successfully separated NFD, LGD, and HGD patients with statistical significance. Whole slide image cytometry is a novel and effective method for the detection of abnormal DNA content in BE. Compared with histological review, it is more objective. Compared with flow cytometry and cytology-preparation image cytometry, it is low cost, simple to use, only requires a single 1 μm section, and facilitates selection of tissue and topographical correlation. Whole slide image cytometry can detect differences in DNA content between NFD, LGD, and HGD patients in this cross-sectional study. Abnormal DNA content detection by whole slide image cytometry is a promising biomarker of progression that could affect future diagnostics in BE.

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Part I: Basic Considerations and Recommendations for Preparation, Measurement and Interpretation

Cited by 111 publications

References 29 publications

DNA Replication Licensing Factors and Aurora Kinases are Linked to Aneuploidy and Clinical Outcome in Epithelial Ovarian Carcinoma

DNA Replication Licensing Factors and Aurora Kinases are Linked to Aneuploidy and Clinical Outcome in Epithelial Ovarian Carcinoma

p53 deficiency exacerbates pleiotropic mitotic defects, changes in nuclearity and polyploidy in transdifferentiating pancreatic acinar cells

Whole slide image cytometry: a novel method to detect abnormal DNA content in Barrett's esophagus

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