High and intermediate grade ductal carcinoma in-situ of the breast: a comparison of pathologic features in core biopsies and excisions and an evaluation of core biopsy features that may predict a close or positive margin in the excision

Ductal carcinoma in-situ (DCIS) of the breast is comprised of a heterogeneous spectrum of intraductal epithelial proliferations that are considered the probable precursor lesions to most invasive breast carcinomas [1,2]. The widespread implementation of screening mammography programs has resulted in a dramatic increase in the incidence of DCIS during the past few decades [3-8]. Whereas most DCIS in the pre-mammographic eras were of the comedo-type, screening-detected DCIS tend to be of a comparatively smaller size and lower grade [9]. Although low-grade and high-grade are unified by the fact that both are intraepithelial proliferations that are breast cancer precursors, they are considered to be substantially different processes. Low-grade DCIS is generally positive for the estrogen & progesterone receptors (ER & PR) and negative for HER2/neu, displays chromosomal losses at 16q, gains in 1q and near euploidy [10,11]. High-grade DCIS, in contrast, tends to display lack of expression of ER and PR, HER2/neu overexpression/amplification, a multitude of chromosomal changes, and aneuploidy [10,11]. Expectedly, intermediate grade DCIS displays changes that are intermediate between these two extremes [10]. Detailed evaluations of the protein expression patterns of DCIS of various grades and a comparison of such patterns with those of their synchronous invasive cancers, typically show strong correlations in a grade-dependent pattern [12]. Furthermore, progression from low-grade to high-grade DCIS is considered to be, at most, a very infrequent event [13]. Therefore, in one contemporary model of the evolution of invasive ductal breast carcinomas, well-differentiated ductal carcinomas evolve from low-grade DCIS whereas poorly differentiated invasive ductal carcinomas evolve from high-grade DCIS, with minimal, if any, overlap [11,13]. The present study focused on DCIS lesions that are not on the lower end of the spectrum to obtain a better understanding of this specific group.S