Nuclear cytometric changes in breast carcinogenesis

Breast cancer is thought to originate through progressively aberrant precur sor lesions, paralleled by increasing morphological changes. The aim of thi s study mas to quantify nuclear features by image cytometry in invasive bre ast cancer and its early hyperplasia and late (ductal carcinoma in situ) pr ecursor lesions, in order to objectively describe nuclear changes in the sp ectrum of proliferative intraductal and invasive breast lesions. Image cyto metry was performed on tissue sections of 20 samples of normal breast tissu e, 71 of usual ductal hyperplasia (UDH), nine of atypical ductal hyperplasi a (ADH), and 11 of well-differentiated and 13 of poorly differentiated duct al carcinoma in situ (DCIS) lesions. The invasive breast carcinomas consist ed of 19 well-differentiated and 24 poorly differentiated lesions, Through the spectrum from normal breast tissue to invasive carcinoma, progressive c hanges in many nuclear features mere measured, Significant differences mere found between nuclei of florid ductal hyperplasia compared with mild and m oderate ductal hyperplastic lesions, suggesting that florid ductal hyperpla sia may be a more advanced lesion than assumed and may contain cancer precu rsor cells, No differences were found between ADH and well-differentiated D CIS, suggesting that these lesions are closely related, Feature values of,w ell-differentiated DCIS were comparable to values found in well-differentia ted invasive carcinoma and the same applied to poorly differentiated DCIS a nd invasive lesions, These results support the hypothesis that breast cance r develops through different routes of progression, one leading to well-dif ferentiated invasive cancer through well-differentiated DCIS, and one leadi ng to poorly differentiated invasive cancer through poorly differentiated D CIS, In conclusion, image cytometry reveals progressive changes in nuclear morphological and subvisual chromatin distribution features in the spectrum from intraductal proliferations to invasive breast cancer, This provides e vidence for a progression from usual to atypical ductal hyperplasia and the n to invasive cancer, through different routes for well-differentiated and poorly differentiated lesions, Copyright (C) 2000 John Whey & Sons, Ltd.