title: Comedo-DCIS is a precursor lesion for basal-like breast carcinoma: identification of a novel p63/Her2/neu expressing subgroup.
abstract: Basal breast cancer comprises ~15% of invasive ductal breast cancers, and presents as high-grade lesions with aggressive clinical behavior. Basal breast carcinomas express p63 and cytokeratin 5 (CK5) antigens characteristic of the myoepithelial lineage, and typically lack Her2/neu and hormone receptor expression. However, there is limited data about the precursor lesions from which they emerge. Here we wished to determine whether comedo-ductal carcinoma in situ (comedo- DCIS), a high-risk in situ breast lesion, serve as precursors for basal-like breast cancer. To determine this link, p63, CK5, Her2/neu, epidermal growth factor receptor (EGFR), estrogen receptor (ER) and progesterone receptor (PgR) expression were analyzed by immunohistochemistry in 17 clinical comedo- and 12 noncomedo-DCIS cases, and in tumors derived from unfractionated and CK5-overexpressing subpopulation (MCF10DCIS.com-CK5(high)) of MCF10DCIS.com cells, a model representative of clinical comedo-DCIS. p63 and Her2/neu coexpression was analyzed by immunofluorescence double labeling. A novel p63/CK5/Her2/neu expressing subpopulation of cells that are ER-/PgR-/EGFR- were identified in the myoepithelial and luminal areas of clinical comedo-DCIS and tumors derived from unfractionated MCF10DCIS.com and MCF10DCIS.com-CK5(high) cells. These data suggest that p63 and Her2/neu expressors may share a common precursor intermediate. P63, but not Her2/neu, expression was significantly associated (P = 0.038) with microinvasion/recurrence of clinical comedo-DCIS, and simultaneous expression of p63 and Her2/neu was marginally associated (P = 0.067) with comedo-DCIS. These data suggest that p63/Her2/neu expressing precursor intermediate in comedo-DCIS may provide a cellular basis for emergence of p63+/Her2/neu- or p63+/Her2/neu+ basal-like breast cancer, and that p63/Her2/neu coexpression may serve as biomarkers for identification of this subgroup of basal-like breast cancers.
authors.affiliation: Department of Oncology, Wayne State University, Detroit, MI, USA. shekharm@karmanos.org
authors.forename: Malathy P V
authors.initials: MP
authors.lastname: Shekhar
authors.forename: Ikuko
authors.initials: I
authors.lastname: Kato
authors.forename: Pratima
authors.initials: P
authors.lastname: Nangia-Makker
authors.forename: Larry
authors.initials: L
authors.lastname: Tait
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D008565:Membrane Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C081876:CKAP4 protein, human
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