Identification of a basal-like subtype of breast ductal carcinoma in situ.
Microarray profiling of invasive breast carcinomas has identified subtypes including luminal A, luminal B, HER2-overexpressing, and basal-like. The poor-prognosis, basal-like tumors have been immunohistochemically characterized as estrogen receptor (ER)-negative, HER2/neu-negative, and cytokeratin 5/6-positive and/or epidermal growth factor receptor (EGFR)-positive. The aim of this study was to determine the prevalence of basal-like ductal carcinoma in situ in a population-based series of cases using immunohistochemical surrogates. A total of 245 pure ductal carcinoma in situ cases from a population-based, case-control study were evaluated for histologic characteristics and immunostained for ER, HER2/neu, EGFR, cytokeratin 5/6, p53, and Ki-67. The subtypes were defined as: luminal A (ER+, HER2-), luminal B (ER+, HER2+), HER2 positive (ER-, HER2+), and basal-like (ER-, HER2-, EGFR+, and/or cytokeratin 5/6+). The prevalence of breast cancer subtypes was basal-like (n = 19 [8%]); luminal A, n = 149 (61%); luminal B, n = 23 (9%); and HER2+/ER-, n = 38 (16%). Sixteen tumors (6%) were unclassified (negative for all 4 defining markers). The basal-like subtype was associated with unfavorable prognostic variables including high-grade nuclei (P < .0001), p53 overexpression (P < .0001), and elevated Ki-67 index (P < .0001). These studies demonstrate the presence of a basal-like in situ carcinoma, a potential precursor lesion to invasive basal-like carcinoma.
Livasy
Chad A
CA
Department of Pathology and Lab Medicine, University of North Carolina, Chapel Hill, NC 27599-7525, USA. cal@med.unc.edu
Perou
Charles M
CM
Karaca
Gamze
G
Cowan
David W
DW
Maia
Diane
D
Jackson
Susan
S
Tse
Chiu-Kit
CK
Nyante
Sarah
S
Millikan
Robert C
RC
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053555:Keratin-5 / Q000032:analysis; D053553:Keratin-6 / Q000032:analysis; D019394:Ki-67 Antigen / Q000032:analysis; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D066246:ErbB Receptors; D053555:Keratin-5; D053553:Keratin-6; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D016159:Tumor Suppressor Protein p53