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| 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
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| 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
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| Overall design |
40 breast cancer consisted of ten each of immunohistochemically ER(+)/HER2(-), ER(+)/HER2(+), ER(-)/HER2(+), and ER(-)/HER2(-) cancers are compared.
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| 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 |
| E-mail(s) |
masuda.shinobu@nihon-u.ac.jp
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| Phone |
81-3-3972-8111
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| Organization name |
Nihon Univeristy School of Medicine
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| Department |
pathology
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| Street address |
30-1 Ohyaguchikami-cho
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| City |
Itabashi |
| State/province |
Tokyo |
| ZIP/Postal code |
173-8610 |
| Country |
Japan |
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| Platforms (1) |
| GPL8300 |
[HG_U95Av2] Affymetrix Human Genome U95 Version 2 Array |
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| Samples (40)
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| GSM135610 |
Human_TK2T_clinically isolated tissue |
| GSM135612 |
Human_TK3T_clinically isolated tissue |
| GSM135614 |
Human_TK4T_clinically isolated tissue |
| GSM135616 |
Human_TK5T_clinically isolated tissue |
| GSM135618 |
Human_TK6T_clinically isolated tissue |
| GSM135620 |
Human_TK9T_clinically isolated tissue |
| GSM135621 |
Human_TK10T_clinically isolated tissue |
| GSM135622 |
Human_TK11T_clinically isolated tissue |
| GSM135623 |
Human_TK12T_clinically isolated tissue |
| GSM135624 |
Human_TK13T_clinically isolated tissue |
| GSM135625 |
Human_TK14T_clinically isolated tissue |
| GSM135626 |
Human_TK15T_clinically isolated tissue |
| GSM135627 |
Human_TK16T_clinically isolated tissue |
| GSM135628 |
Human_TK17T_clinically isolated tissue |
| GSM135629 |
Human_TK18T_clinically isolated tissue |
| GSM135630 |
Human_TK19T_clinically isolated tissue |
| GSM135631 |
Human_TK20T_clinically isolated tissue |
| GSM135632 |
Human_TK21T_clinically isolated tissue |
| GSM135633 |
Human_TK22T_clinically isolated tissue |
| GSM135634 |
Human_TK23T_clinically isolated tissue |
| GSM135635 |
Human_TK24T_clinically isolated tissue |
| GSM135636 |
Human_TK25T_clinically isolated tissue |
| GSM135637 |
Human_TK26T_clinically isolated tissue |
| GSM135638 |
Human_TK27T_clinically isolated tissue |
| GSM135639 |
Human_TK28T_clinically isolated tissue |
| GSM135640 |
Human_TK29T_clinically isolated tissue |
| GSM135641 |
Human_TK30T_clinically isolated tissue |
| GSM135642 |
Human_TK31T_clinically isolated tissue |
| GSM135643 |
Human_TK32T_clinically isolated tissue |
| GSM135644 |
Human_TK33T_clinically isolated tissue |
| GSM135645 |
Human_TK34T_clinically isolated tissue |
| GSM135646 |
Human_TK35T_clinically isolated tissue |
| GSM135647 |
Human_TK36T_clinically isolated tissue |
| GSM135648 |
Human_TK37T_clinically isolated tissue |
| GSM135649 |
Human_TK38T_clinically isolated tissue |
| GSM135650 |
Human_TK39T_clinically isolated tissue |
| GSM135651 |
Human_TK40T_clinically isolated tissue |
| GSM135652 |
Human_TK41T_clinically isolated tissue |
| GSM135653 |
Human_TK42T_clinically isolated tissue |
| GSM135654 |
Human_TK43T_clinically isolated tissue |
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| Relations |
| BioProject |
PRJNA99585 |
| 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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