- Paper Report
- Open Access
Nuclear cytometric changes in breast carcinogenesis
- Syed Mohsin1
© Current Science Ltd 2000
- Published: 1 December 2000
- image analysis
- in situ carcinoma
- premalignant breast lesions
Image morphometry has been shown to provide useful information in several types of human tumors, including breast. Image cytometry can identify preinvasive lesions in human cervix with malignant potential and may predict response in patients with prostate and renal carcinoma. In breast cancer, it has been shown that morphometric data correlates with several important biological factors, including hormone receptors and p53 status. However, premalignant mammary lesions have not been studied in a systematic fashion using this technique.
To study quantitated nuclear morphological features of the entire spectrum of human premalignant breast lesions including UDH, atypical ductal hyperplasia (ADH), DCIS and IC.
Modified Fuelgen staining was performed on 71 UDH, 9 ADH, 24 DCIS and 43 IC. Intermediately differentiated DCIS and IC were excluded. About 50-300 non-overlapping nuclei were imaged on a Cyto-Savant imaging device. Nuclear features (n = 128) were analyzed in the following categories; morphometric, photometric, discrete texture, Markovian texture, fractal texture and run length texture features. Normal lymphocytes were used as internal diploid controls.
Nuclei in more advanced lesions generally displayed the following features: they were larger; were more pleomorphic; showed a reduced area with high density chromatin; showed decreased contrast; showed increased fractal area; and showed increased mean value of optical intensity. The lesions could be divided into three groups with similar features: (1) normal epithelium (from reduction mammoplasties), mild and moderate UDH; (2) florid UDH, ADH, well differentiated DCIS and well differentiated IC, and (3) poorly differentiated DCIS and high grade IC. DNA index showed that florid UDH is polyclonal and some of these lesions contain aneuploid clones. Of the 128 nuclear features studied, 56 were significantly different between well and poorly differentiated DCIS and IC.
This study suggests that morphometric characteristics of epithelial cells in the terminal duct lobular unit are similar to those in mild and moderate UDH. Some florid UDH contain aneuploid cell population and may represent biologically more advanced lesions. Similar morphometric features of ADH and well differentiated DCIS suggest that these two lesions are nearly equally advanced and may differ is size only. Features of ADH, well differentiated DCIS and IC are remarkably different from poorly differentiated DCIS and IC and support the hypothesis of direct biologic progression in these categories.