title: Proteomics of human breast ductal carcinoma in situ.
abstract: We report the first proteomic analysis of matched normal ductal/lobular units and ductal carcinoma in situ (DCIS) of the human breast. An understanding of the transition from normal epithelium to the first definable stage of cancer at the functional level of protein expression is hypothesized to contribute to improved detection, prevention, and treatment. Ten sets of two-dimensional gels were evaluated, containing either matched normal ductal/lobular units or DCIS from either whole tissue sections or up to 100,000 laser capture microdissected epithelial cells. Differential protein expression was confirmed by image analysis. Protein spots (315) were excised and subjected to mass spectrometry sequencing. Fifty-seven proteins were differentially expressed between normal ductal/lobular units and DCIS. Differences in overall protein expression levels and posttranslational processing were evident. Ten differentially expressed proteins were validated in independent DCIS specimens, and 14 of 15 proteomic trends from two-dimensional gel analyses were confirmed by standard immunohistochemical analysis using a limited independent tumor cohort. Many of the proteins identified were previously unconnected with breast cancer, including proteins regulating the intracellular trafficking of membranes, vesicles, cancer preventative agents, proteins, ions, and fatty acids. Other proteomic identifications related to cytoskeletal architecture, chaperone function, the microenvironment, apoptosis, and genomic instability. Proteomic analysis of DCIS revealed differential expression patterns distinct from previous nucleic acid-based studies and identified new facets of the earliest stage of breast cancer progression.
authors.affiliation: Women's Cancers Section, Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland 20892, USA.
authors.forename: Julia D
authors.initials: JD
authors.lastname: Wulfkuhle
authors.forename: Dennis C
authors.initials: DC
authors.lastname: Sgroi
authors.forename: Henry
authors.initials: H
authors.lastname: Krutzsch
authors.forename: Kelley
authors.initials: K
authors.lastname: McLean
authors.forename: Kelly
authors.initials: K
authors.lastname: McGarvey
authors.forename: Melodie
authors.initials: M
authors.lastname: Knowlton
authors.forename: She
authors.initials: S
authors.lastname: Chen
authors.forename: Hongjun
authors.initials: H
authors.lastname: Shu
authors.forename: Aysegul
authors.initials: A
authors.lastname: Sahin
authors.forename: Raffael
authors.initials: R
authors.lastname: Kurek
authors.forename: Diethelm
authors.initials: D
authors.lastname: Wallwiener
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Merino
authors.forename: Emanuel F
authors.initials: EF
authors.lastname: Petricoin
authors.forename: Yingming
authors.initials: Y
authors.lastname: Zhao
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Steeg
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002278:Carcinoma in Situ / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000473:pathology; D018275:Carcinoma, Lobular / Q000378:metabolism / Q000473:pathology; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D007150:Immunohistochemistry; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D040901:Proteomics / Q000379:methods*
chemical_list: D009363:Neoplasm Proteins