Next-generation Sequencing

A Powerful Tool for the Discovery of Molecular Markers in Breast Ductal Carcinoma In Situ

Hitchintan Kaur; Shihong Mao; Seema Shah; David H Gorski; Stephen A Krawetz; Bonnie F Sloane; Raymond R Mattingly

Disclosures

Expert Rev Mol Diagn. 2013;13(2):151-165. 

In This Article

Models of DCIS Progression to Invasive Breast Cancer

Several models have been proposed based on epidemiological, morphological and immunohistochemical studies to describe the progression from noninvasive DCIS to invasive breast carcinoma (Figure 1). The traditional linear model of progression hypothesizes that the progression occurs sequentially in stages from normal epithelium to invasive carcinoma through hyperplasia and in situ carcinoma. Genomic and transcriptomic studies provide further support for this multistep progression model. In the classic 'ductal' model proposed by Wellings and Jensen, flat epithelial atypia, atypical ductal hyperplasia (ADH) and DCIS are nonobligate precursors of IDC. The postulates of this theory are that DCIS is a direct precursor of IDC and that ADH is a direct precursor to low-grade DCIS.[21] In 'nonlinear' or 'branched' models, DCIS is a progenitor of IDC, yet different grades of DCIS progress to corresponding grades of IDC. In contrast, the 'parallel' model of progression of DCIS and IDC hypothesizes that DCIS and IDC diverge from a common progenitor cell and progress independently through different grades in parallel.[22] Strong evidence that DCIS and IDC develop from a common clonal origin and then can continue to evolve in parallel comes from a study of copy number variations in coexisting DCIS and IDC from patient samples[23] and from the long-appreciated clinical observation that IDC is frequently accompanied by DCIS.

Figure 1.

Models of malignant progression of normal breast epithelium to carcinoma. Evidence from epidemiological, morphological and immunohistochemical studies has been used to develop several models to describe the progression from noninvasive DCIS to IDC. (A) A linear model that suggests that progression occurs in sequential steps from normal epithelium to invasive carcinoma via hyperplasia and in situ carcinoma. The postulates of this hypothesis include that DCIS is a direct precursor of IDC and that atypical ductal hyperplasia is a direct precursor to low-grade DCIS. (B) In 'nonlinear' or 'branched' models, DCIS is a progenitor of IDC, yet different grades of DCIS progress to corresponding grades of IDC. The low, intermediate and high grades can also be termed grades I, II and III, respectively. There may also be further progression of IDC. (C) The 'parallel' model of progression hypothesizes that DCIS and IDC diverge from a common progenitor cell and progress independently through different grades in parallel.DCIS: Ductal carcinoma in situ; IDC: Invasive ductal carcinoma.

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