Karyometry of the Colonic Mucosa

Alberts, David S.; Einspahr, Janine G.; Krouse, Robert S.; Ranger‐Moore, James; Hamilton, Peter; Lance, Peter; Goldschmid, Steven; Hess, Lisa M.; Yozwiak, Michael; Bartels, Hubert G.; Bartels, Peter H.

doi:10.1158/1055-9965.epi-07-0595

Cited by 24 publications

(22 citation statements)

References 20 publications

(17 reference statements)

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“…Our study builds upon numerous earlier efforts that have applied digital nuclear morphometry to questions involving risk and prognosis in cancer of the breast [10], cervix [2], oropharynx/lung [11], colon [12], skin [13] and prostate. In the prostate, nuclear morphometry has been shown to detect abnormalities in benign tissue adjacent to cancer and HGPIN [14], [15].…”

Section: Discussionmentioning

confidence: 99%

Development of a Nuclear Morphometric Signature for Prostate Cancer Risk in Negative Biopsies

et al. 2013

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BackgroundOur objective was to develop and validate a multi-feature nuclear score based on image analysis of direct DNA staining, and to test its association with field effects and subsequent detection of prostate cancer (PCa) in benign biopsies.MethodsTissue sections from 39 prostatectomies were Feulgen-stained and digitally scanned (400×), providing maps of DNA content per pixel. PCa and benign epithelial nuclei were randomly selected for measurement of 52 basic morphometric features. Logistic regression models discriminating benign from PCa nuclei, and benign from malignant nuclear populations, were built and cross-validated by AUC analysis. Nuclear populations were randomly collected <1 mm or >5 mm from cancer foci, and from cancer-free prostates, HGPIN, and PCa Gleason grade 3–5. Nuclei also were collected from negative biopsy subjects who had a subsequent diagnosis of PCa and age-matched cancer-free controls (20 pairs).ResultsA multi-feature nuclear score discriminated cancer from benign cell populations with AUCs of 0.91 and 0.79, respectively, in training and validation sets of patients. In prostatectomy samples, both nuclear- and population-level models revealed cancer-like features in benign nuclei adjacent to PCa, compared to nuclei that were more distant or from PCa-free glands. In negative biopsies, a validated model with 5 variance features yielded significantly higher scores in cases than controls (P = 0.026).ConclusionsA multifeature nuclear morphometric score, obtained by automated digital analysis, was validated for discrimination of benign from cancer nuclei. This score demonstrated field effects in benign epithelial nuclei at varying distance from PCa lesions, and was associated with subsequent PCa detection in negative biopsies.ImpactThis nuclear score shows promise as a risk predictor among men with negative biopsies and as an intermediate biomarker in Phase II chemoprevention trials. The results also suggest that subvisual disturbances in nuclear structure precede the development of pre-neoplastic lesions.

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Section: Discussionmentioning

confidence: 99%

Development of a Nuclear Morphometric Signature for Prostate Cancer Risk in Negative Biopsies

et al. 2013

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“…An adenoma on colonoscopy represents a higher risk of future neoplasia (metachronous lesions) thus providing the biological underpinnings behind post-polypectomy surveillance colonoscopy 10 . A number of other biomarkers of field carcinogenesis in endoscopically-normal mucosa have been reported including rectal aberrant crypt foci (ACF) 11 , proliferation 12 , decreased apoptosis 13 , nuclear karyometry 14 , and genomic (microarray) 15 , proteomic 16 , methylation 17 , TGF-α 18 , and crypt-restricted cytochrome C oxidase subunit I 19 markers. However, the diagnostic performance of current biomarkers has been suboptimal.…”

Section: Field Carcinogenesismentioning

confidence: 99%

Light-Scattering Technologies for Field Carcinogenesis Detection: A Modality for Endoscopic Prescreening

Backman

Roy

2011

Gastroenterology

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Colonoscopy has revolutionized colorectal cancer (CRC) screening resulting in a decrease in both CRC mortality and incidence. Despite this, CRC still ranks as the second leading cause of cancer deaths among Americans underscoring the need to both increase availability and accuracy of colonoscopy. The latter considerations provide the impetus for much of the current research into adjunctive imaging technologies. Recent advances in improving detection of dysplasia that have translated into clinical practice include high-definition scopes, narrow-band imaging, and chromo-endoscopy. Another major direction of research into improving endoscopy is determining histology of lesions in situ (“optical biopsy”) with confocal endomicroscopy, fluorescence and elastic scattering spectroscopy. All these techniques are of great promise in improving delivery of endoscopy but, to date, have not addressed the potentially more important hurdle associated with logistic challenges of providing accurate CRC screening for the entire at-risk population.

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“…Changes in nuclear morphology also may be important early in the carcinogenic process, and this includes the nuclear features of colonic epithelial cells such as size, variability in size, and circularity that are altered to a large extent in malignancy and dysplasia [16]. Since nuclei become more elliptical as cells stop proliferating and move up the crypt, nuclear features may be related to the proliferative state of cells [17].…”

Section: Introductionmentioning

confidence: 99%

Effects of a Mediterranean Diet Intervention on Anti- and Pro-Inflammatory Eicosanoids, Epithelial Proliferation, and Nuclear Morphology in Biopsies of Normal Colon Tissue

Djurić

Turgeon

Ren

et al. 2015

Nutrition and Cancer

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This randomized trial evaluated the effects of intervention with either a Healthy Eating or a Mediterranean diet on colon biomarkers in 120 healthy individuals at increased colon cancer risk. The hypothesis was that eicosanoids and markers of proliferation would be favorably affected by the Mediterranean diet. Colon epithelial biopsy tissues and blood samples were obtained at baseline and after six months of intervention. Colonic eicosanoid concentrations were evaluated by HPLC-MS-MS, and measures of epithelial proliferation and nuclear morphology were evaluated by image analysis of biopsy sections. There was little change in pro-inflammatory eicosanoids and in plasma cytokine concentrations with either dietary intervention. There was, however, a 50% increase in colonic prostaglandin E3 (PGE3), which is formed from eicosapentanoic acid, in the Mediterranean arm. Unlike PGE2, PGE3, was not significantly affected by regular use of non-steroidal anti-inflammatory drugs at baseline, and normal weight subjects had significantly higher colon PGE3 than overweight or obese subjects. Increased proliferation in the colon at baseline, by Ki67 labeling, was associated with morphological features that defined smaller nuclei in the epithelial cells, lower colon leukotriene concentrations and higher plasma cytokine concentrations. Dietary intervention had little effect on measures of epithelial proliferation or of nuclear morphology. The increase in PGE3 with a Mediterranean diet indicates that in normal colon, diet might affect protective pathways to a greater extent than pro-inflammatory and proliferative pathways. Hence, biomarkers from cancer models might not be relevant in a true prevention setting.

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Karyometry of the Colonic Mucosa

Cited by 24 publications

References 20 publications

Development of a Nuclear Morphometric Signature for Prostate Cancer Risk in Negative Biopsies

Development of a Nuclear Morphometric Signature for Prostate Cancer Risk in Negative Biopsies

Light-Scattering Technologies for Field Carcinogenesis Detection: A Modality for Endoscopic Prescreening

Effects of a Mediterranean Diet Intervention on Anti- and Pro-Inflammatory Eicosanoids, Epithelial Proliferation, and Nuclear Morphology in Biopsies of Normal Colon Tissue

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