title: Differential proteomic analysis of late-stage and recurrent breast cancer from formalin-fixed paraffin-embedded tissues.
abstract: The heterogeneity of breast cancer requires the discovery of more incisive molecular tools that better define disease progression and prognosis. Proteomic analysis of homogeneous tumor cell populations derived by laser microdissection from formalin-fixed, paraffin-embedded (FFPE) tissues has proven to be a robust strategy for conducting retrospective cancer biomarker investigations. We describe an MS-based analysis of laser microdissected cancerous epithelial cells derived from twenty-five breast cancer patients at defined clinical disease stages with the goal of identifying protein abundance characteristics indicative of disease progression and recurrence. Comparative analysis of stage 0 and stage III patients revealed 113 proteins that significantly differentiated these groups and included known factors associated with disease pathogenesis, such as CDH1 and CTNNB1, as well as those previously implicated in breast cancer, such as TSP-1. Similar analyses of patients presenting with stage II disease that did or did not exhibit recurrence two years postdiagnosis revealed 42 proteins that significantly differentiated these subgroups and included IRS-1 and PARK7. These data provide evidence supporting the utility of FFPE tissues for functional proteomic analyses and protein biomarker discovery and yielded protein candidates indicative of disease stage and recurrence in breast cancer that warrant further investigation for diagnostic utility and biological relevance.
authors.affiliation: Department of Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Bateman
authors.forename: Mai
authors.initials: M
authors.lastname: Sun
authors.forename: Rohit
authors.initials: R
authors.lastname: Bhargava
authors.forename: Brian L
authors.initials: BL
authors.lastname: Hood
authors.forename: Marlene M
authors.initials: MM
authors.lastname: Darfler
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Kovatich
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Hooke
authors.forename: David B
authors.initials: DB
authors.lastname: Krizman
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Conrads
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology* / Q000517:prevention & control; D002853:Chromatography, Liquid / Q000379:methods; D018450:Disease Progression; D005260:Female; D005404:Fixatives; D005557:Formaldehyde; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D016612:Paraffin Embedding; D020543:Proteome / Q000032:analysis*; D012008:Recurrence; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; D005404:Fixatives; D009363:Neoplasm Proteins; D020543:Proteome; D005557:Formaldehyde