Immunohistochemical categorisation of ductal carcinoma in situ of the breast

Abstract

The aim of this study is to analyse whether immunohistochemistry (IHC) applying a broad set of markers could be used to categorise ductal carcinoma in situ (DCIS) of the breast in distinct subgroups corresponding to the recently defined molecular categories of invasive carcinoma. Immunohistochemistry of pure DCIS cases constructed in tissue arrays was performed with 16 markers (oestrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), Bcl-2, p53, Her2, insulin-like growth factor receptor, E-cadherin, epithelial membrane antigen (EMA), CA125, keratins 5/6, 14, 19, epidermal growth factor receptor, S100, and CD31). Results in 163 cases were analysed by unsupervised hierarchical clustering. Histological classification was performed by review of whole tissue sections and identified 36 well-, 55 intermediately, and 72 poorly differentiated DCISs. Unsupervised hierarchical cluster analysis categorised DCIS into two major groups that could be further subdivided into subgroups based on the expression of six markers (ER, PR, AR, Bcl-2, p53, and Her2). In the major predominantly ER/Bcl-2-positive (luminal) group, three subgroups (ARpositive (n ¼ 33), AR-negative (n ¼ 40), and mixed (n ¼ 34)) could be identified and included 34 well-differentiated DCISs. Within the major predominantly ER/Bcl-2-negative (nonluminal) group, a Her2-positive subgroup (n ¼ 34) was characterised by 31 poorly differentiated lesions. Eight triple-negative lesions, including one positive for keratin 5/6 and two positive for p53, were encountered. Intermediately differentiated DCIS shared a comparable IHC staining pattern with well-differentiated DCIS that was distinct from poorly differentiated DCIS (Po0.001). Ductal carcinoma in situ could be categorised by IHC into two major groups and five subgroups using six markers. Morphologically, intermediately differentiated DCIS seems to have more biological similarities with well-differentiated lesions as compared to poorly differentiated lesions.

Premalignant Breast Neoplasia: A Paradigm of Interlesional and Intralesional Molecular Heterogeneity and Its Biological and Clinical Ramifications

“…HER2 overexpression seems to be most significant in high-grade DCIS, in which its prevalence is nearly 75% (17). In contrast to this relatively higher prevalence of HER2 overexpression in DCIS, the prevalence of marker expression indicative of the basal-like subtype is relatively lower in DCIS compared with IDC (1,3,4,17,18).…”

“…An increased prevalence of HER2 protein overexpression (and gene amplification) in DCIS versus IDC has been confirmed in a number of subsequent studies (1,(16)(17)(18). HER2 overexpression seems to be most significant in high-grade DCIS, in which its prevalence is nearly 75% (17). In contrast to this relatively higher prevalence of HER2 overexpression in DCIS, the prevalence of marker expression indicative of the basal-like subtype is relatively lower in DCIS compared with IDC (1,3,4,17,18).…”

“…For example, Allred et al initially observed that human epidermal growth factor receptor 2 (HER2) is overexpressed at a higher frequency in DCIS than in IDC (15). An increased prevalence of HER2 protein overexpression (and gene amplification) in DCIS versus IDC has been confirmed in a number of subsequent studies (1,(16)(17)(18). HER2 overexpression seems to be most significant in high-grade DCIS, in which its prevalence is nearly 75% (17).…”

Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists

“…[101][102][103][104][105][106][107] However, it should be noted that its prevalence is lower than that of invasive triplenegative and basal-like breast cancers and that triple-negative and basal-like cancers often lack an overt in situ component. Whether this is the result of basal-like and triple-negative breast cancers progressing rapidly from DCIS to invasive cancer and/or obliterating the DCIS precursor from which they arose remains a matter of speculation.…”

Androgen Receptor (AR) and Breast Cancer: Reference to the AR Status in Normal/Benign Breast Luminal Cells

“…Depending on the methodology and study population, AR positivity in breast carcinomas has been reported ranging from 50% to 90%, with the similar staining intensity as ER [11][12][13] . While most of the ER-positive breast carcinomas are also positive for AR [14] , AR is also positive in some of the triple negative and high grade breast carcinomas, even though the reported percentage is considerably variable among different studies (ranging from 0-53%) [11,12,[14][15][16][17] . Furthermore, studies have shown that the AR expression in breast carcinomas is clinically relevant.…”