Ductal carcinoma in situ of the breast (DCIS) with heterogeneity of nuclear grade: prognostic effects of quantitative nuclear assessment
1 National Cancer Institute of Canada Clinical Trials Group, Queen's University, 10 Stuart Street, Kingston, Ontario K7L 3N6, Canada
2 Department of Pathology, University Health Network and University of Toronto, Princess Margaret Hospital, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada
3 Henrietta Banting Breast Centre, Women's College Hospital, University of Toronto, 76 Grenville Street, 7th floor, Toronto, Ontario M5S 1B2, Canada
4 Department of Statistics and Actuarial Science, Faculty of Mathematics, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1, Canada
5 Equipoise Imaging LLC, 4009 St. Johns Lane, Ellicott City, MD 21042, USA
6 Department of Mathematics and Statistics, York University, 4700 Keele Street, Toronto, Ontario M3J 1P3, Canada
7 Department of Genetics and Cancer Institute of New Jersey, Rutgers University, 604 Allison Road, Piscataway, NJ 08854-8082, USA
BMC Cancer 2007, 7:174 doi:10.1186/1471-2407-7-174Published: 10 September 2007
Previously, 50% of patients with breast ductal carcinoma in situ (DCIS) had more than one nuclear grade, and neither worst nor predominant nuclear grade was significantly associated with development of invasive carcinoma. Here, we used image analysis in addition to histologic evaluation to determine if quantification of nuclear features could provide additional prognostic information and hence impact prognostic assessments.
Nuclear image features were extracted from about 200 nuclei of each of 80 patients with DCIS who underwent lumpectomy alone, and received no adjuvant systemic therapy. Nuclear images were obtained from 20 representative nuclei per duct, from each of a group of 5 ducts, in two separate fields, for 10 ducts. Reproducibility of image analysis features was determined, as was the ability of features to discriminate between nuclear grades. Patient information was available about clinical factors (age and method of DCIS detection), pathologic factors (DCIS size, nuclear grade, margin size, and amount of parenchymal involvement), and 39 image features (morphology, densitometry, and texture). The prognostic effects of these factors and features on the development of invasive breast cancer were examined with Cox step-wise multivariate regression.
Duplicate measurements were similar for 89.7% to 97.4% of assessed image features. For the pooled assessment with ~200 nuclei per patient, a discriminant function with one densitometric and two texture features was significantly (p < 0.001) associated with nuclear grading, and provided 78.8% correct jackknifed classification of a patient's nuclear grade. In multivariate assessments, image analysis nuclear features had significant prognostic associations (p ≤ 0.05) with the development of invasive breast cancer. Texture (difference entropy, p < 0.001; contrast, p < 0.001; peak transition probability, p = 0.01), densitometry (range density, p = 0.004), and measured margin (p = 0.05) were associated with development of invasive disease for the pooled data across all ducts.
Image analysis provided reproducible assessments of nuclear features which quantitated differences in nuclear grading for patients. Quantitative nuclear image features indicated prognostically significant differences in DCIS, and may contribute additional information to prognostic assessments of which patients are likely to develop invasive disease.