Please confirm you are human (Sign Up for free to never see this)
← Back to Search
Ductal Carcinoma In Situ And The Emergence Of Diversity During Breast Cancer Evolution
D. Allred, Y. Wu, Sufeng Mao, I. Nagtegaal, S. Lee, C. M. Perou, S. Mohsin, P. O'Connell, A. Tsimelzon, D. Medina
Published 2008 · Biology, Medicine
Save to my Library
Download PDFAnalyze on Scholarcy
Purpose: Human invasive breast cancers (IBC) show enormous histologic and biological diversity. This study comprehensively evaluated diversity in ductal carcinoma in situ (DCIS), the immediate precursors of IBCs. Experimental Design: The extent of diversity for conventional histologic grade and standard prognostic biomarkers assessed by immunohistochemistry was evaluated in a series of pure DCIS (n = 200) compared with a contemporaneous series of IBCs (n = 200). A subset of the DCIS (n = 25) was evaluated by DNA microarrays for the presence of luminal, basal, and erbB2 intrinsic subtypes. The extent of diversity within individual cases of DCIS (n = 120) was determined by assessing multiple regions independently for histologic (nuclear) grade and several biomarkers by immunohistochemistry, which approximate microarrays in determining intrinsic subtypes. Results: DCIS showed a broad distribution of conventional histologic grades and standard biomarkers ranging from well to poorly differentiated, nearly identical to IBCs. Microarrays showed the same intrinsic subtypes in DCIS as in IBCs. However, higher resolution analysis showed that multiple histologic grades, biomarker phenotypes, and intrinsic subtypes often coexist within the same DCIS, and these diverse regions probably compete for dominance. Diversity within cases of DCIS was highly correlated with mutated p53 (P = 0.0007). Conclusions: These results support the hypothesis that poorly differentiated DCIS gradually evolve from well-differentiated DCIS by randomly acquiring genetic defects resulting in increasingly abnormal cellular features. This diversity is amplified by defects resulting in genetic instability (e.g., p53 mutation), and the alterations are propagated to IBC in a manner independent of progression to invasion.
This paper references
Carcinoma in situ of the breast: correlation of histopathology to immunohistochemical markers and DNA ploidy
G. Ottesen (2004)
Repeated observation of breast tumor subtypes in independent gene expression data sets
T. Sørlie (2003)
Her-2/neu overexpression and response to oophorectomy plus tamoxifen adjuvant therapy in estrogen receptor-positive premenopausal women with operable breast cancer.
R. Love (2003)
Molecular evolution of breast cancer
P. Simpson (2005)
Diseases of the Breast
C. Haagensen (1971)
Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications
T. Sørlie (2001)
Pathologic features of breast cancers in women with previous benign breast disease.
T. Jacobs (2001)
Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma
C. Livasy (2006)
The clinical behavior of breast carcinoma is Probably determined at the preinvasive stage (Ductal carcinoma in Situ)
S. Gupta (1997)
The multistep nature of cancer.
B. Vogelstein (1993)
Conservation of Breast Cancer Molecular Subtypes and Transcriptional Patterns of Tumor Progression Across Distinct Ethnic Populations
Kun Yu (2004)
Comparison of loss heterozygosity in primary and recurrent ductal carcinoma in situ of the breast.
R. Lininger (1998)
Ductal carcinoma in situ of the breast. Heterogeneity of individual lesions
W. Lennington (1994)
Neu-protein overexpression in breast cancer. Association with comedo-type ductal carcinoma in situ and limited prognostic value in stage II breast cancer.
M. J. van de Vijver (1988)
Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer: a validation study
Syed K Mohsin (2004)
Stem Cells,Cancer and Cancer Stem Cells
Zang Ai-hua (2005)
Genetic abnormalities in mammary ductal intraepithelial neoplasia‐flat type (“clinging ductal carcinoma in situ”)
F. Moinfar (2000)
Different clinical impact of estradiol receptor determination according to the analytical method: a study on 1940 breast cancer patients over a period of 16 consecutive years
N. Magne (2005)
Biologic features of human premalignant breast disease
D C Allred (2004)
Association of p53 protein expression with tumor cell proliferation rate and clinical outcome in node-negative breast cancer.
D. Allred (1993)
Genetically Engineered Mouse Models of Mammary Intraepithelial Neoplasia
R. Cardiff (2004)
Cancer as an evolutionary and ecological process
L. M. Merlo (2006)
Molecular portraits of human breast tumours
C. Perou (2000)
Gene expression profiles of human breast cancer progression
X. Ma (2003)
Xenograft Models of Premalignant Breast Disease
F. Miller (2004)
Ductal carcinoma in situ of the breast: correlation between histologic classifications and biologic markers.
A. Moreno (1997)
Fifteen-year results of breast-conserving surgery and definitive breast irradiation for the treatment of ductal carcinoma in situ of the breast.
L. Solin (1996)
:A long term follow-up study
S. Shidahara (1982)
Accumulation of mutant p53 is associated with increased proliferation and poor clinical outcome in node-negative breast cancer
D C Allred (1993)
Atypical hyperplastic lesions of the female breast. A long‐term follow‐up study
D. Page (1985)
SEER Cancer Statistics Review 1975^2000. Bethesda: National Cancer Institute
Lag Ries (2003)
The multistep nature of cancer.Trends Genet1993;9:138^41
B Vogelstein (1993)
Association with comedo-type ductal carcinoma in situ and limited prognostic value in stage II breast cancer
M J Van De Vijver (1988)
Ductal carcinoma-in-situ of the breast
HazelM. Thornton (1992)
Mammary stem cells, self-renewal pathways, and carcinogenesis
S. Liu (2005)
In situ analyses of genome instability in breast cancer
K. Chin (2004)
Classification of ductal carcinoma in situ by gene expression profiling
J. Hannemann (2006)
An atlas of subgross pathology of the human breast with special reference to possible precancerous lesions.
S. Wellings (1975)
The clonal evolution of tumor cell populations.
P. Nowell (1976)
Overexpression of HER-2/neu and its relationship with other prognostic factors change during the progression of in situ to invasive breast cancer.
D. Allred (1992)
Hormones, receptors, and growth in hyperplastic enlarged lobular units: early potential precursors of breast cancer
Sangjun Lee (2005)
pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long‐term follow‐up
C. Elston (1991)
Columnar Cell Lesions of the Breast: The Missing Link in Breast Cancer Progression?: A Morphological and Molecular Analysis
P. Simpson (2005)
Accumulation of p53 protein as a possible predictor of response to adjuvant combination chemotherapy with cyclophosphamide, methotrexate, fluorouracil, and prednisone for breast cancer.
R. Elledge (1995)
Pathological prognostic factors in breast cancer.
C. Elston (1999)
Amplification of mRNA populations using aRNA generated from immobilized oligo(dT)-T7 primed cDNA.
J. Eberwine (1996)
An evaluation of six antibodies for immunohistochemistry of mutant p53 gene product in archival colorectal neoplasms
I. Baas (1994)
Biologic markers in ductal carcinoma in situ and concurrent infiltrating carcinoma. A comparison of eight contemporary grading systems.
A. Leong (2001)
Duct carcinoma in situ: 227 cases without microinvasion.
M. Silverstein (1992)
Immunohistochemical and Clinical Characterization of the Basal-Like Subtype of Invasive Breast Carcinoma
T. Nielsen (2004)
Identification of a basal-like subtype of breast ductal carcinoma in situ.
C. Livasy (2007)
Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer.
J. Harvey (1999)
Genetic abnormalities in mammary intraepithelial neoplasia-flat type (''cloning ductal carcinoma in situ''): a simulator of normal mammary epithelium
F Moinfar (2000)
Pathology of preinvasive and excellent-prognosis breast cancer.
D. Page (1996)
Ductal carcinoma in situ and the emergence of diversity during breast cancer evolution
DC Allred (2008)
Relationship of a new histological categorization of ductal carcinoma in situ of the breast with size and the immunohistochemical expression of p53, c-erb B2, bcl-2, and ki-67.
L. Mack (1997)
Antisense RNA Amplification: A Linear Amplification Method for Analyzing the mRNA Population from Single Living Cells
Prognostic and predictive factors in breast cancer by immunohistochemical analysis.
D. Allred (1998)
Analysis of loss of heterozygosity in 399 premalignant breast lesions at 15 genetic loci.
P. O'Connell (1998)
The Preneoplastic Phenotype in Murine Mammary Tumorigenesis
D. Medina (2004)
Molecular markers in ductal carcinoma in situ of the breast.
D. Porter (2003)
Increases in ductal carcinoma in situ (DCIS) of the breast in relation to mammography: a dilemma.
V. Ernster (1997)
On the origin and progression of ductal carcinoma in the human breast.
S. Wellings (1973)
Characterization of extensive genetic alterations in ductal carcinoma in situ by fluorescence in situ hybridization and molecular analysis.
D. Murphy (1995)
Benign Breast Disease and Breast Cancer Risk: Morphology and Beyond
S. Schnitt (2003)
Stem cells in mammary development and carcinogenesis
G. Dontu (2007)
Estrogen receptor-positive proliferating cells in the normal and precancerous breast.
B. Shoker (1999)
Control of genomic instability and epithelial tumor development by the p53-Fbxw7/Cdc4 pathway.
J. Perez-losada (2005)
Ductal carcinoma in situ of the breast: reproducibility of histological subtype analysis.
M. Scott (1997)
Method for grading breast cancer.
E. W. Elston (1993)
Patterns of Chromosomal Alterations in Breast Ductal Carcinoma In situ
E. S. Hwang (2004)
Pathology of preinvasive and excellent prognosis breast cancer.
J. Simpson (2001)
Stem Cells and Cancer: Two Faces of Eve
M. Clarke (2006)
Genetic clonal diversity predicts progression to esophageal adenocarcinoma
C. Maley (2006)
Use of immuno-LCM to identify the in situ expression profile of cellular constituents of the tumor microenvironment
R. Buckanovich (2006)
Histopathologic Types of Benign Breast Lesions and the Risk of Breast Cancer: Case–Control Study
A. Shaaban (2002)
The pathology of invasive breast cancer A Syllabus Derived from Findings of the National Surgical Adjuvant Breast Project (Protocol No. 4)
Edwin R. Fisher (1975)
This paper is referenced by
Evolutionary Dynamics Unifies Carcinogenesis and Cancer Therapy
R. Gillies (2014)
Molecular Markers as Prognostic Factors in DCIS and Small Invasive Breast Cancers.
N. Saenger (2014)
Molecular pathology of pre-invasive breast disease in the screening setting: Application in diagnosis and management
Amy E. McCart Reed (2012)
FGFR1 is amplified during the progression of in situ to invasive breast carcinoma
M. Jang (2012)
Does Microenvironment Contribute to the Etiology of Estrogen Receptor–Negative Breast Cancer?
M. Barcellos-Hoff (2013)
Molecular subtyping of DCIS: heterogeneity of breast cancer reflected in pre-invasive disease
S. E. Clark (2011)
Molecular Features of Subtype-Specific Progression from Ductal Carcinoma In Situ to Invasive Breast Cancer.
Robert Lesurf (2016)
Immune Escape in Breast Cancer During In Situ to Invasive Carcinoma Transition.
C. R. Gil del Alcazar (2017)
Genomic Assays in Ductal Carcinoma In Situ: Implications for Management Decisions
A. Gangi (2017)
The effect of imidazo [1,2-a] pyridine amines on MCF-7 and MDA-MB-231 breast cancer cells
T. Kurebwa (2015)
Biomarqueurs de cancer et leurs procédés d'utilisation
Karla Kerlikowske (2011)
Biology of DCIS and Progression to Invasive Disease
Sanaz A. Jansen (2012)
Epigenetic regulation of amino acids metabolic genes defines targets of synthetic lethality in breast cancer
F. Cavicchioli (2014)
Polysomy 17 and HER-2 amplification: true, true, and unrelated.
Carol L. Rosenberg (2008)
Opportunities for molecular epidemiological research on ductal carcinoma in-situ and breast carcinogenesis: interdisciplinary approaches.
M. Sherman (2014)
Evolutionary dynamics of carcinogenesis and why targeted therapy does not work
R. Gillies (2012)
Computer-Based Image Studies on Tumor Nests Mathematical Features of Breast Cancer and Their Clinical Prognostic Value
Lin-Wei Wang (2013)
A mouse mammary tumor virus env-like exogenous sequence is strictly related to progression of human sporadic breast carcinoma.
C. Mazzanti (2011)
NCCN Task Force Report: Estrogen Receptor and Progesterone Receptor Testing in Breast Cancer by Immunohistochemistry.
D. Allred (2009)
Pathology and Biological Markers of Invasive Breast Cancer
Rodrigo Gonçalves (2014)
Modeling Human Ductal Carcinoma In Situ in the Mouse
F. Behbod (2018)
HER-2/neu Overexpression as a Predictor for the Transition from In situ to Invasive Breast Cancer
R. Roses (2009)
Microenvironmental Control of the Breast Cancer Cell Cycle
X. Guo (2012)
Molecular Genetics of Ductal Carcinoma In Situ and Lobular Carcinoma In Situ
Jorge S. Reis-Filho (2011)
Breast Cancer Stem Cells: How to Target These Chameleons - Masters of Disguise
Geetika Chakravarty (2012)
Appraisal of the technologies and review of the genomic landscape of ductal carcinoma in situ of the breast
J. Pang (2015)
Pathomimetic avatars reveal divergent roles of microenvironment in invasive transition of ductal carcinoma in situ
M. Sameni (2017)
Ductal Carcinoma In Situ Biology, Biomarkers, and Diagnosis
K. Gorringe (2017)
Preinvasive breast cancer.
D. Sgroi (2010)
Ductal carcinoma in situ (DCIS): pathological features, differential diagnosis, prognostic factors and specimen evaluation
S. Pinder (2010)
Asthma in the 21st Century — Unexpected Applications of Ancient Treatments
P. Pundir (2013)
Cellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotype.
S. Y. Park (2010)See more