Karyometry in the early detection and chemoprevention of intraepithelial lesions

Ranger‐Moore, James; Alberts, David S.; Montironi, Rodolfo; Garcia, F.; Davis, John R.; Frank, Denise; Brewer, Molly; Mariuzzi, G.M.; Bartels, Hubert G.; Bartels, Peter H.

doi:10.1016/j.ejca.2005.07.002

Cited by 12 publications

(10 citation statements)

References 13 publications

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“…In normal tissue, the height of each bar is f0.65, which is the typical mean absolute deviation in a Gaussian distribution. Tissues experiencing progression to cancer show marked increases in z value for numerous karyometric features (26).…”

Section: Karyometric Analysismentioning

confidence: 99%

“…Progression to cancer is revealed as a positive skew in the lesion signature because progression is accompanied by increasing numbers of nuclei deviating notably from normal. The average nuclear abnormality, computed as the mean over the abnormality values of all nuclei in a sample from a given lesion, is a useful measure of lesion progression (16,26).…”

Section: Karyometric Analysismentioning

confidence: 99%

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Karyometry of the Colonic Mucosa

Alberts¹,

Einspahr²,

Krouse

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Objective: The study summarizes results of karyometric measurements in epithelial cells of the colorectal mucosa to document evidence of a field effect of preneoplastic development among patients with colorectal adenocarcinoma or adenoma. Methods: Karyometric analyses were done on highresolution images of histologic sections from 48 patients with colorectal adenocarcinomas and 44 patients with adenomas and on images from matching normal-appearing mucosa directly adjacent to such lesions, at a 1-cm and 10-cm distance from the lesions or from the rectal mucosa of adenoma patients, as well as from 24 healthy normal controls with no family history of colonic disease. Results:The nuclei recorded in the histologically normal-appearing mucosa of patients with either colorectal adenoma or adenocarcinoma exhibited differences in karyometric features in comparison with nuclei recorded in rectal mucosa from patients who were free of a colonic lesion. These differences were expressed to the same extent in tissue adjacent to the lesions and in normal-appearing tissue as distant as the rectum. Conclusions: The nuclear chromatin pattern may serve as an integrating biomarker for a preneoplastic development. The field effect might provide an end point in chemopreventive intervention trials. (Cancer Epidemiol Biomarkers Prev 2007;16(12):2704 -16)

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Section: Karyometric Analysismentioning

confidence: 99%

Section: Karyometric Analysismentioning

confidence: 99%

Karyometry of the Colonic Mucosa

Alberts¹,

Einspahr²,

Krouse

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…One may define a fixed numerical value for a criterion and use, as a measure of agent efficacy, the proportion of nuclei or cases, which at the end of study have returned to below that value. One may also choose to take advantage of a progression curve and accept as evidence of agent efficacy the reduction of deviation from normal, in a given case, downward along the progression curve whether a fixed criterion value was reached at the end of the study or not (2). This latter measure is possibly more realistic and certainly more sensitive for a detection of efficacy.…”

Section: Introductionmentioning

confidence: 99%

Limits of Detection of Chemopreventive Efficacy: Karyometry of Skin Biopsies

Bartels¹,

Yozwiak²,

Bartels³

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Objective: This study was designed to establish estimates of the smallest effects due to chemopreventive intervention detectable by karyometry in skin biopsies. Methods: Estimates of the smallest change of statistical significance and estimates of the power of the test were derived for several key features descriptive of the distribution of nuclear chromatin. Results from triplicate biopsies from the same case were used to provide estimates of the within-case, biopsy-to-biopsy variance. Results: Generally, a change in feature value due to chemopreventive intervention can be statistically secured when it amounts to 5% to 10%. In clinical trials where matched baseline and end of study biopsies from the same cases are available, paired comparison ANOVA can detect a 2% change on samples of 25 cases. Establishing efficacy in individual cases requires a change in feature values on the order of 10% to 15%. Conclusions: Karyometry provides a sensitive, quantitative method for the assessment of efficacy of chemoprevention. The effects of within-case, biopsy-to-biopsy variance need to be considered only in the evaluation of individual cases and are on the order of 5% in skin biopsies. (Cancer Epidemiol Biomarkers Prev 2008; 17(7):1689 -95)

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“…Ki-67 expression was low, as expected for postmenopausal women with benign disease [16,19]. Previous karyometric studies have shown early field effect changes [20,21]; therefore, very early changes revealed by karyometry might be seen here in compromised or at-risk cell clusters. At this point, it is also important to note that there may be a proportion of disrupted cells that show reduced or no Ki-67 expression, yet harbor significant genetic abnormalities as found in a study of in situ breast cancer cells by Man et al [22].…”

Section: Discussionmentioning

confidence: 73%

Digital image analysis of breast epithelial cells collected by random periareolar fine-needle aspirates (RPFNA) from women at high risk for breast cancer taking hormone replacement and the aromatase inhibitor, letrozole, for six months

Frank

Kimler

Fabian

et al. 2009

Breast Cancer Res Treat

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Aromatase inhibitors are currently being evaluated as preventive agents in post-menopausal women at high risk for breast cancer. A phase II trial of 42 women on hormone replacement therapy (HRT) treated with letrozole for 6 months showed Ki-67 was reduced by 66% but showed no change in cytomorphology or Masood score. Subsequent image analytical procedures (karyometry) conducted on a subset of the samples captured subvisual information that showed reduced cellular abnormality after 6 months of letrozole. In the present study we expanded on the preliminary karyometry study to determine if the change in karyometric measurements corresponded to changes in risk biomarkers quantified in the Phase II trial; and secondly, whether these biomarkers might be used together to serve as markers of response in individual cases. Pap stained slides from the Phase II trial were used. Epithelial cell images were digitized on a CCD video-microphotometer and the nuclei were segmented from the field using a semiautomatic algorithm. Nine out of 37 cases analyzed showed a numerical decrease in all three markers, although only three of these exhibited changes substantial enough to be considered as an improvement. However, 12 cases showed improvement by cytology (a decrease in Masood score of at least 2), an additional 13 cases demonstrated a reduction in Ki-67 expression by 50% of the median baseline value, and an additional five cases exhibited a decrease of at least 10% in abnormal cells by nuclear morphometry. Thus, a total of 30 of 37 cases (81%) showed improvement in at least one marker. There was no correlation between changes in Ki-67%, karyometric abnormality, and Masood score change other than specimens that exhibited an improvement in cytology also displayed greater decreases in nuclear morphometry abnormalities. Given the heterogeneity of mechanisms leading to malignancy, the quantitative analysis of nuclear chromatin patterns may be valuable as a global, or integrating, biomarker of change in chemoprevention studies in conjunction with additional markers. Correlation with long term clinical outcome is needed to validate meaningful combinations of informative biomarkers.

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Karyometry in the early detection and chemoprevention of intraepithelial lesions

Cited by 12 publications

References 13 publications

Karyometry of the Colonic Mucosa

Karyometry of the Colonic Mucosa

Limits of Detection of Chemopreventive Efficacy: Karyometry of Skin Biopsies

Digital image analysis of breast epithelial cells collected by random periareolar fine-needle aspirates (RPFNA) from women at high risk for breast cancer taking hormone replacement and the aromatase inhibitor, letrozole, for six months

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