Quantitative Study of Breast Cancer Progression: Different Pathways for Various In Situ Cancers

Abstract

Breast cancer is known to progress through multiple, genomic changes (1-11). These accumulating changes result in the nuclear alterations on which the pathologic diagnosis and microscopic prognosis of cancer are based. The natural history of ductal breast cancer is, even today, only incompletely known. The suggestion that a clonal selection (12) occurs in the progression from atypical hyperplasia toward ductal carcinoma in situ (DCIS) and invasive cancers seems to be supported by recent cytogenetic and molecular studies (1,13,14) and also by the characteristic morphological heterogeneity (15) of various ductal proliferative premalignant lesions. We studied alterations of the nuclear chromatin pattern concomitant with the development of different histologically defined diagnostic categories in ductal proliferative lesion progression. Recent work led to the development of methods allowing a more extensive use of information extracted from diagnostic imagery. One such method is the characterization of individual nuclei, of sets of nuclei, and of entire lesions by a "signature." These signatures are based on a substantial number of karyometric features, for each of which a measure of deviation from "normal" is computed. The deviation values are arranged in the form of a profile (16).In earlier studies, these procedures were applied to images of nuclei from ductal proliferating breast lesions and DCIS (17,18). It was shown that nuclei from a number of the conventional diagnostic categories of proliferating breast lesions representing breast cancer progression are characterized by a monotonically increasing nuclear abnormality. The histologically defined subjective diagnostic categories, ordered by relative risk for development of

Molecular profile of atypical hyperplasia of the breast

“…The chromosomal changes seen in atypical hyperplasias are similar to those present in breast cancer [16][17][18], and are consistent with the proposal that AHs are preneoplastic lesions and part of a continuum in the steps toward breast cancer [19,20]. Mariuzzi et al [17] examined the nuclear chromatin pattern in AH and found drastic changes in karyometric features, with these changes similar to those seen in comedo DCIS. Others have noted a high incidence of monoclonality (51.3%) in ADH [21], and an abnormal DNA content [6], consistent with neoplastic transformation.…”

Quantitative characterization of preneoplastic progression using single‐cell computed tomography and three‐dimensional karyometry

“…Improvements in powerful imaging and data analysis technologies have facilitated the development of quantitative nuclear morphometry as a sensitive tool to identify malignancy associated changes for a variety of cancer types (5,8,13,14,34). Previous studies have demonstrated the potential of automated biosignature feature extraction to classify or monitor neoplastic progression stage using a variety of methods.…”

Evaluation of pathways for progression of heterogeneous breast tumors

“…Although these observations are consistent with DCIS being a progenitor of IDC, they do not exclude the possibility that DCIS and IDC may have a common progenitor and progress in separate lineages. Observations that have been interpreted specifically as consistent with independent progression of DCIS and IDC have included measurements of nuclear morphometry (Mommers et al, 2001a;Mariuzzi et al, 2002) and microsatellite markers (Fujii et al, 1996;Lichy et al, 2000).…”