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Series GSE6367 Query DataSets for GSE6367
Status Public on Mar 14, 2009
Title Gene profile of breast cancers with immunohistochemical phenotypes of ER+/- and/or HER2+/-
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Hormones and growth factors accelerate cell proliferation of breast cancer cells, and these molecules are well investigated targets for drug development and application. The mechanisms of cell proliferation of breast cancers lacking estrogen receptor (ER) and HER2 have not been fully understood. The purpose of the present study is to find genes that are differentially expressed in breast cancers and that might significantly contribute to cell proliferation in these cancers. Forty tumor samples, consisting of ten each of immunohistochemically ER(+)/HER2(-), ER(+)/HER2(+), ER(-)/HER2(+), and ER(-)/HER2(-) cancer were analyzed using oligonucleotide microarrays. Both genes and tumor samples were subjected to hierarchical clustering. ER(+)/HER2(-) breast cancers and ER(-)/HER2(-) cancers tended to form a tumor cluster, but HER2 positive breast cancers were split into different tumor clusters.
Significant differential expression between IHC-ER(-)/HER2(-) and other tumors was defined as having an expression level at least 2-fold higher or 2-fold lower, and analyzed by multi-step two-way ANOVA. Genes overexpressed differently in IHC-ER(-)/HER2(-) breast cancers compared to other all three types were 8 genes (FABP7, GABRP, GAL, CXCL13, CDC42EP4, C2F, FOXM1, CSDA), and underexpressed genes were nine including ITGB5, KIAA0310, MAGED2, PRSS11, SORL1, TGFB3, KRT18, CPE, BCAS1. No gene was directly related to cell proliferation such as cyclins, cyclin-dependent kinase, p53, p16, and the pRb and p21 families. We had a particular focus on a transcriptional factor E2F-5 from a list of genes overexpressed in ER negative breast cancers compared to ER positive breast cancers, and further examined.
Gene amplification of E2F-5 was detected in 5/57 (8.8%) in breast cancers by FISH. No point mutation was found at the binding domain with DNA or dimerization partner of E2F-5. Immunohistochemically E2F-5 positive cancers were more frequent in ER(-)/HER2(-) cancer (14/27, 51.9%) than in other types of cancer (5/30, 16.7%) (p=0.05). E2F-5 positive cancers had higher Ki-67 labeling index (59.5%) than E2F-5 negative cancers (36.3%). E2F-5 positive cancers showed higher histological grade including metaplastic carcinoma, and worse clinical outcome with shorter disease free survival in node negative patients. In conclusion, we demonstrated that there is a population of breast cancer with overexpression of a cell cycle related transcriptional factor E2F-5. E2F-5 positive breast cancers were frequent in ER(-)/HER2(-) group with high Ki-67 labeling index, high histological grade and worse clinical outcome.
Keywords: immunohistochemical phenotype
Overall design 40 breast cancer consisted of ten each of immunohistochemically ER(+)/HER2(-), ER(+)/HER2(+), ER(-)/HER2(+), and ER(-)/HER2(-) cancers are compared.
Contributor(s) Shirane M, Takekoshi S, Tokuda Y, Mori K, Osamura YR
Citation(s) 19259095, 22537114
Submission date Nov 26, 2006
Last update date Nov 24, 2020
Contact name shinobu Masuda
Phone 81-3-3972-8111
Organization name Nihon Univeristy School of Medicine
Department pathology
Street address 30-1 Ohyaguchikami-cho
City Itabashi
State/province Tokyo
ZIP/Postal code 173-8610
Country Japan
Platforms (1)
GPL8300 [HG_U95Av2] Affymetrix Human Genome U95 Version 2 Array
Samples (40)
GSM135610 Human_TK2T_clinically isolated tissue
GSM135612 Human_TK3T_clinically isolated tissue
GSM135614 Human_TK4T_clinically isolated tissue
BioProject PRJNA99585

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE6367_RAW.tar 113.0 Mb (http)(custom) TAR (of CEL)
GSE6367_TK_series_pathological_data.xlsx 13.1 Kb (ftp)(http) XLSX
Processed data included within Sample table

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