Identification of a basal-like subtype of breast ductal carcinoma in situ

Livasy, Chad; Perou, Charles M.; Karaca, Gamze; Cowan, David P.; Maia, Diane M.; Jackson, Susan; Tse, Chiu Kit; Nyante, Sarah J.; Millikan, Robert C.

doi:10.1016/j.humpath.2006.08.017

Cited by 189 publications

(186 citation statements)

References 28 publications

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“…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).…”

Section: Interlesional Heterogeneity Of Premalignant Lesionsmentioning

confidence: 89%

“…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).…”

Section: Interlesional Heterogeneity Of Premalignant Lesionsmentioning

confidence: 99%

“…DCIS has long been known to be heterogeneous in its morphologic features, presentation, and clinical behavior. The emergence of genomic and gene expression profiling has established that DCIS is heterogeneous at a level of molecular complexity that is comparable with or perhaps greater than that of invasive disease (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). Although certainly less studied, the heterogeneity observed in the microenvironment surrounding individual premalignant lesions may also be a critical determinant of their future behavior.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Berman

Gauthier

Tlsty

2010

Cancer Prevention Research

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As is well established in invasive breast disease, it is becoming increasingly clear that molecular heterogeneity, both between and within lesions, is a prevalent, distinct phenotype of premalignant lesions of the breast. Key pathways of tumorigenesis modulate critical features of premalignant lesions such as proliferation, differentiation, stress response, and even the generation of diversity. Current studies show that evaluation of these lesions may provide clinically useful information on future tumor formation as well as biological insights into the origin and functional significance of this distinct phenotype. Cancer Prev Res; 3(5); 579-87. ©2010 AACR.

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Section: Interlesional Heterogeneity Of Premalignant Lesionsmentioning

confidence: 89%

Section: Interlesional Heterogeneity Of Premalignant Lesionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Berman

Gauthier

Tlsty

2010

Cancer Prevention Research

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“…This could be a result of the interobserver variability, since our cutoff point was more than 10% strong membraneous staining, while Bryan et al (2006) considered any staining as positive. Recently, (Livasy et al (2007) found 8% basal-like subtypes in a population-based series of 245 patients. Given that invasive breast cancers typically share immunophenotypic features with the DCIS lesion from which they arise, these findings corroborate the possibility that the triplenegative DCIS lesions represent a precursor lesion to invasive basal-like carcinomas.…”

Section: Immunohistochemical Categorisation Of Dcis P Meijnen Et Almentioning

confidence: 99%

Immunohistochemical categorisation of ductal carcinoma in situ of the breast

et al. 2007

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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.

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“…Low-grade DCIS is associated with ER positivity and luminal phenotypes, while high-grade DCIS is associated with negative ER, positive HER2, and 7 the basal-like phenotype [26]. The basal-like subtype seems to be associated with a higher risk of local recurrence than are luminal subtypes, and may even have stronger and more consistent associations than some of the conventional histopathological factors [10,27].…”

Section: Molecular Pathology Of Dcismentioning

confidence: 98%