Nuclear chromatin characteristics of breast solid pattern ductal carcinoma in situ
To characterize nuclei from breast solid pattern ductal carcinoma in situ (DCIS) by their karyometric features and to search for the presence of statistically significantly different subsets of nuclei.
One hundred nuclei from each of 6 normal, 13 solid DCIS, (9 low and intermediate grade and 4 high grade DCIS) histopathologic samples of breast tissue were digitally recorded. Karyometric features were computed and subjected to a nonsupervised learning algorithm (P-index) to identify significantly different subgroups.
Nuclei in low grade lesions displayed a diploid/near diploid pattern, while the majority of intermediate grade lesions fell into a range beyond 5N. The high grade lesions showed substantial genomic instability and represented three statistically different subsets or phenotypes.
There is a progression of nuclear abnormality from low grade to high grade DCIS. The nuclei from high grade DCIS form a heterogeneous set that represents three phenotypes. One of these phenotypes shows a nuclear chromatin pattern that more closely resembles poorly differentiated, infiltrating disease. The observation of such a phenotype may have prognostic implications.
Available from: Yuejiao Fu
- "Computer-aided image analysis is such a method. Image analysis has been used to extract quantitative nuclear information useful for diagnosis of biopsy specimens of many tissues, including breast DCIS, and invasive breast (Kerlikowske et al. 2003; Carpenter et al. 1985; Dey et al. 2000; Frank et al. 2001; Hoque et al. 2001; Mariuzzi et al. 1996; Mommers et al. 2001; Susnik et al. 1995; Tuczek et al. 1996; Wolberg et al. 1995). However, these previous reports did not focus on evaluating information for individual nuclei in the classifi cation of patients with mixed nuclear grades. "
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ABSTRACT: Nuclear grade has been associated with breast DCIS recurrence and progression to invasive carcinoma; however, our previous study of a cohort of patients with breast DCIS did not find such an association with outcome. Fifty percent of patients had heterogeneous DCIS with more than one nuclear grade. The aim of the current study was to investigate the effect of quantitative nuclear features assessed with digital image analysis on ipsilateral DCIS recurrence.
Hematoxylin and eosin stained slides for a cohort of 80 patients with primary breast DCIS were reviewed and two fields with representative grade (or grades) were identified by a Pathologist and simultaneously used for acquisition of digital images for each field. Van Nuys worst nuclear grade was assigned, as was predominant grade, and heterogeneous grading when present. Patients were grouped by heterogeneity of their nuclear grade: Group A: nuclear grade 1 only, nuclear grades 1 and 2, or nuclear grade 2 only (32 patients), Group B: nuclear grades 1, 2 and 3, or nuclear grades 2 and 3 (31 patients), Group 3: nuclear grade 3 only (17 patients). Nuclear fine structure was assessed by software which captured thirty-nine nuclear feature values describing nuclear morphometry, densitometry, and texture. Step-wise forward Cox regressions were performed with previous clinical and pathologic factors, and the new image analysis features.
Duplicate measurements were similar for 89.7% to 97.4% of assessed image features. The rate of correct classification of nuclear grading with digital image analysis features was similar in the two fields, and pooled assessment across both fields. In the pooled assessment, a discriminant function with one nuclear morphometric and one texture feature was significantly (p = 0.001) associated with nuclear grading, and provided correct jackknifed classification of a patient's nuclear grade for Group A (78.1%), Group B (48.4%), and Group C (70.6%). The factors significantly associated with DCIS recurrence were those previously found, type of initial presentation (p = 0.03) and amount of parenchymal involvement (p = 0.05), along with the morphometry image feature of ellipticity (p = 0.04).
Analysis of nuclear features measured by image cytometry may contribute to the classification and prognosis of breast DCIS patients with more than one nuclear grade.
Available from: Denise H Frank
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ABSTRACT: The chromatin pattern in nuclei from breast ductal proliferative lesions was quantitatively evaluated with the objective of deriving measures of tumor progression. A total of 110 cases were analyzed. There were 38 cases of normal tissue or benign proliferative lesions, 41 cases of ductal carcinoma in situ (DCIS), and 31 cases of microinfiltrating DCIS and of infiltrating cancer. A total of 9424 nuclei were analyzed. High-resolution images were digitally recorded. For each nucleus, 93 karyometric features descriptive of the spatial and statistical distribution of the nuclear chromatin were computed. Data analysis included establishing a profile of relative deviations of each feature from "normal," called the nuclear signature, and of lesion signatures as well as of trends of lesion progression. Two trends of evolution could be discerned: one from normal to hyperplasia, atypical hyperplasia, and comedo DCIS as representative of high-grade lesions; and the other from normal to hyperplasia to cribriform DCIS, solid DCIS, and infiltrating cancer, representing lower grade lesions. The nuclei in microinfiltrating foci are distinctly different from nuclei in high-grade comedo DCIS. The nuclei in microinfiltrating foci have a statistically significantly lower nuclear abnormality. They may represent outgrowing clones.
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ABSTRACT: To characterize, by morphometric and chromatin texture analysis, a series of rectal carcinomas classified according to Dukes staging.
High-resolution imagery of 6,001 nuclei from 51 specimens of rectal carcinoma and 22 specimens of normal rectal tissue was digitally recorded. A set of 93 features descriptive of the spatial and statistical distribution of nuclear chromatin was computed for each nucleus to form a characteristic signature.
Rectal carcinomas were significantly different from normal rectum in their digital signature. Eleven karyometric features, such as nuclear area and total optical density, were clearly different between the groups, with significant differences found in analysis of 8 of those features. The most distinctive pattern in lesion signatures in comparison with normal rectal tissue was observed at Dukes' stage D. However, the highest average signature values were seen at Dukes' stage B. The lesion signatures and total optical density observed in cancer specimens deviated markedly from values in the normal group.
Chromatin texture signature proved to be a useful method of identifying and characterizing nuclear differences between rectal carcinoma and normal rectal tissue.
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