Abstract

Nuclear morphometry is a method for quantitative measurement of histopathologic changes in the appearance of stained cell nuclei. Numerous studies have indicated that these assessments may provide clinically relevant information related to the degree of progression and malignant potential of breast neoplasia. Nuclear features are derived from computerized analysis of digitized microscope images, and a quantitative Feulgen stain for DNA was used. Features analyzed included: (1) DNA content; (2) nuclear size and shape; and (3) texture features, describing spatial features of chromatin distribution. In this study replicated measurements are described on a series of 54 breast carcinoma specimens of differing pathologic grades. Duplicate measurements were performed using two serial sections, which were processed and analyzed separately. The value of a single feature measurement, the nuclear area profile, was shown to be the strongest indicator of progression. A quantitative nuclear grade was derived and shown to be strongly correlated with not only the pathologic nuclear grade, but also with tubule formation, mitotic grade, and with the overall histopathologic grade. Analysis of replication precision showed that the standard methods of the histopathology laboratory, if practiced in a uniform manner, are sufficient to ensure reproducibility of these assessments. We argue that nuclear morphometry provides a standardized and reproducible framework for quantitative pathologic assessments.

Highlights

  • Nuclear morphometry relates to the computerized analysis of digital microscope images of stained cell nuclei, and is used to characterize pathological changes in the appearance of neoplastic cells

  • Promising intermediate endpoints have been identified for breast carcinoma progression, and include elements of the Nottingham prognostic index, cytometric DNA content, receptors of the EGF-Erb-B family, estrogen receptors, TGF-alpha, p53, PCNA, and other proteins involved in control of proliferation

  • In this report we show that this method provides a quantitative framework for pathologic assessments, and may be useful in the definition of a continuous index of progression for breast carcinoma

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Summary

Introduction

Nuclear morphometry relates to the computerized analysis of digital microscope images of stained cell nuclei, and is used to characterize pathological changes in the appearance of neoplastic cells. Promising intermediate endpoints have been identified for breast carcinoma progression, and include elements of the Nottingham prognostic index, cytometric DNA content, receptors of the EGF-Erb-B family, estrogen receptors, TGF-alpha, p53, PCNA, and other proteins involved in control of proliferation (reviewed in [2]). In this context, nuclear morphometry is an attractive biomarker since it is a direct and quantitative measure of an established prognostic marker in breast tissue: the pathologic appearance of the stained cell nucleus. In this report we show that this method provides a quantitative framework for pathologic assessments, and may be useful in the definition of a continuous index of progression for breast carcinoma

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