title: Epithelial cells captured from ductal carcinoma in situ reveal a gene expression signature associated with progression to invasive breast cancer.
abstract: Breast cancer biomarkers that can precisely predict the risk of progression of non-invasive ductal carcinoma in situ (DCIS) lesions to invasive disease are lacking. The identification of molecular alterations that occur during the invasion process is crucial for the discovery of drivers of transition to invasive disease and, consequently, biomarkers with clinical utility. In this study, we explored differences in gene expression in mammary epithelial cells before and after the morphological manifestation of invasion, i.e., early and late stages, respectively. In the early stage, epithelial cells were captured from both pre-invasive lesions with distinct malignant potential [pure DCIS as well as the in situ component that co-exists with invasive breast carcinoma lesions (DCIS-IBC)]; in the late stage, epithelial cells were captured from the two distinct morphological components of the same sample (in situ and invasive components). Candidate genes were identified using cDNA microarray and rapid subtractive hybridization (RaSH) cDNA libraries and validated by RT-qPCR assay using new samples from each group. These analyses revealed 26 genes, including 20 from the early and 6 from the late stage. The expression profile based on the 20 genes, marked by a preferential decrease in expression level towards invasive phenotype, discriminated the majority of DCIS samples. Thus, this study revealed a gene expression signature with the potential to predict DCIS progression and, consequently, provides opportunities to tailor treatments for DCIS patients.
authors.affiliation: Laboratory of Genomics and Molecular Biology, CIPE-International Research Center, A.C. Camargo Cancer Center, São Paulo, SP, Brazil.
authors.forename: Eliana Vanina
authors.initials: EV
authors.lastname: Elias
authors.affiliation: Laboratory of Genomics and Molecular Biology, CIPE-International Research Center, A.C. Camargo Cancer Center, São Paulo, SP, Brazil.
authors.forename: Nadia Pereira
authors.initials: NP
authors.lastname: de Castro
authors.affiliation: Laboratory of Genomics and Molecular Biology, CIPE-International Research Center, A.C. Camargo Cancer Center, São Paulo, SP, Brazil.
authors.forename: Paulo Henrique Baldan
authors.initials: PH
authors.lastname: Pineda
authors.affiliation: Laboratory of Genomics and Molecular Biology, CIPE-International Research Center, A.C. Camargo Cancer Center, São Paulo, SP, Brazil.
authors.forename: Carolina Sens
authors.initials: CS
authors.lastname: Abuázar
authors.affiliation: Department of Anatomical Pathology, A.C. Camargo Cancer Center, São Paulo, SP, Brazil.
authors.forename: Cynthia Aparecida
authors.initials: CA
authors.lastname: Bueno de Toledo Osorio
authors.affiliation: Laboratory of Genomics and Molecular Biology, CIPE-International Research Center, A.C. Camargo Cancer Center, São Paulo, SP, Brazil.
authors.forename: Mabel Gigliola
authors.initials: MG
authors.lastname: Pinilla
authors.affiliation: Laboratory of Genomics and Molecular Biology, CIPE-International Research Center, A.C. Camargo Cancer Center, São Paulo, SP, Brazil.
authors.forename: Sabrina Daniela
authors.initials: SD
authors.lastname: da Silva
authors.affiliation: Ludwig Institute for Cancer Research, São Paulo, SP, Brazil.|Molecular Oncology Center, Sirio-Libanese Hospital, São Paulo, SP, Brazil.
authors.forename: Anamaria Aranha
authors.initials: AA
authors.lastname: Camargo
authors.affiliation: Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, SP, Brazil.
authors.forename: Wilson Araujo
authors.initials: WA
authors.lastname: Silva
authors.affiliation: Laboratory of Genomics and Molecular Biology, CIPE-International Research Center, A.C. Camargo Cancer Center, São Paulo, SP, Brazil.
authors.forename: Elisa Napolitano
authors.initials: EN
authors.lastname: E Ferreira
authors.affiliation: Institute of Psychiatry-Medical School, University of São Paulo (FMUSP), São Paulo, SP, Brazil.
authors.forename: Helena Paula
authors.initials: HP
authors.lastname: Brentani
authors.affiliation: Laboratory of Genomics and Molecular Biology, CIPE-International Research Center, A.C. Camargo Cancer Center, São Paulo, SP, Brazil.|National Institute of Science and Technology in Oncogenomics (INCITO), São Paulo, SP, Brazil.
authors.forename: Dirce Maria
authors.initials: DM
authors.lastname: Carraro
mesh_terms: D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002278:Carcinoma in Situ / Q000235:genetics* / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology*; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D056726:Genetic Association Studies; D006801:Humans; D009367:Neoplasm Staging; D015203:Reproducibility of Results; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor
keywords: breast cancer; cellular-based analysis; ductal carcinoma in situ progression; gene signature; molecular markers