Identification of molecular apocrine breast tumours by microarray analysis

被引:575
作者
Farmer, P
Bonnefoi, H
Becette, V
Tubiana-Hulin, M
Fumoleau, P
Larsimont, D
MacGrogan, G
Bergh, J
Cameron, D
Goldstein, D
Duss, S
Nicoulaz, AL
Brisken, C
Fiche, M
Delorenzi, M
Iggo, R [1 ]
机构
[1] Swiss Inst Bioinformat, Lausanne, Switzerland
[2] Swiss Inst Expt Canc Res, Natl Ctr Competence Res Mol Oncol, CH-1066 Epalinges, Switzerland
[3] Hop Univ Geneve, Geneva, Switzerland
[4] Swiss Grp Clin Canc Res, Bern, Switzerland
[5] Eortc Data Ctr, European Org Res Treatment Canc, Brussels, Belgium
[6] Ctr Rene Gauducheau, F-44035 Nantes, France
[7] Ctr Rene Huguenin, St Cloud, France
[8] Inst Jules Bordet, B-1000 Brussels, Belgium
[9] Inst Bergonie, Bordeaux, France
[10] Karolinska Inst, Swedish Breast Canc Grp, Stockholm, Sweden
[11] Univ Edinburgh, ACCOG, Edinburgh, Midlothian, Scotland
[12] CHU Vaudois, CH-1011 Lausanne, Switzerland
关键词
breast cancer; microarrays; apocrine carcinoma;
D O I
10.1038/sj.onc.1208561
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Previous microarray studies on breast cancer identified multiple tumour classes, of which the most prominent, named luminal and basal, differ in expression of the oestrogen receptor a gene ( ER). We report here the identification of a group of breast tumours with increased androgen signalling and a 'molecular apocrine' gene expression pro. le. Tumour samples from 49 patients with large operable or locally advanced breast cancers were tested on Affymetrix U133A gene expression microarrays. Principal components analysis and hierarchical clustering split the tumours into three groups: basal, luminal and a group we call molecular apocrine. All of the molecular apocrine tumours have strong apocrine features on histological examination (P = 0.0002). The molecular apocrine group is androgen receptor (AR) positive and contains all of the ER-negative tumours outside the basal group. Kolmogorov-Smirnov testing indicates that oestrogen signalling is most active in the luminal group, and androgen signalling is most active in the molecular apocrine group. ERBB2 amplification is commoner in the molecular apocrine than the other groups. Genes that best split the three groups were identified by Wilcoxon test. Correlation of the average expression pro. le of these genes in our data with the expression pro. le of individual tumours in four published breast cancer studies suggest that molecular apocrine tumours represent 8-14% of tumours in these studies. Our data show that it is possible with microarray data to divide mammary tumour cells into three groups based on steroid receptor activity: luminal (ER+AR+), basal (ER+AR+) and molecular apocrine (ER+AR+).
引用
收藏
页码:4660 / 4671
页数:12
相关论文
共 51 条
[31]   EGFR mutations in lung cancer:: Correlation with clinical response to gefitinib therapy [J].
Paez, JG ;
Jänne, PA ;
Lee, JC ;
Tracy, S ;
Greulich, H ;
Gabriel, S ;
Herman, P ;
Kaye, FJ ;
Lindeman, N ;
Boggon, TJ ;
Naoki, K ;
Sasaki, H ;
Fujii, Y ;
Eck, MJ ;
Sellers, WR ;
Johnson, BE ;
Meyerson, M .
SCIENCE, 2004, 304 (5676) :1497-1500
[32]   Hypoxia induces the expression of a 43-kDa protein (PROXY-1) in normal and malignant cells [J].
Park, H ;
Adams, MA ;
Lachat, P ;
Bosman, F ;
Pang, SC ;
Graham, CH .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 276 (01) :321-328
[33]   Distinctive gene expression patterns in human mammary epithelial cells and breast cancers [J].
Perou, CM ;
Jeffrey, SS ;
Van de Rijn, M ;
Rees, CA ;
Eisen, MB ;
Ross, DT ;
Pergamenschikov, A ;
Williams, CF ;
Zhu, SX ;
Lee, JCF ;
Lashkari, D ;
Shalon, D ;
Brown, PO ;
Botstein, D .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (16) :9212-9217
[34]   Molecular portraits of human breast tumours [J].
Perou, CM ;
Sorlie, T ;
Eisen, MB ;
van de Rijn, M ;
Jeffrey, SS ;
Rees, CA ;
Pollack, JR ;
Ross, DT ;
Johnsen, H ;
Akslen, LA ;
Fluge, O ;
Pergamenschikov, A ;
Williams, C ;
Zhu, SX ;
Lonning, PE ;
Borresen-Dale, AL ;
Brown, PO ;
Botstein, D .
NATURE, 2000, 406 (6797) :747-752
[35]   Microarray analysis reveals a major direct role of DNA copy number alteration in the transcriptional program of human breast tumors [J].
Pollack, JR ;
Sorlie, T ;
Perou, CM ;
Rees, CA ;
Jeffrey, SS ;
Lonning, PE ;
Tibshirani, R ;
Botstein, D ;
Borresen-Dale, AL ;
Brown, PO .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (20) :12963-12968
[36]  
ROSEN PP, 1996, DIS BREAST, P413
[37]   SILHOUETTES - A GRAPHICAL AID TO THE INTERPRETATION AND VALIDATION OF CLUSTER-ANALYSIS [J].
ROUSSEEUW, PJ .
JOURNAL OF COMPUTATIONAL AND APPLIED MATHEMATICS, 1987, 20 :53-65
[38]   ENDOCRINE TREATMENT OF BREAST-CANCER IN WOMEN [J].
SANTEN, RJ ;
MANNI, A ;
HARVEY, H ;
REDMOND, C .
ENDOCRINE REVIEWS, 1990, 11 (02) :221-265
[39]   Oncogenes, granules and breast cancer: what has c-myc to do with apocrine changes? [J].
Schmitt, FC ;
Reis, JS .
BREAST, 2002, 11 (06) :463-465
[40]  
Selim AGA, 2000, J PATHOL, V191, P138, DOI 10.1002/(SICI)1096-9896(200006)191:2<138::AID-PATH611>3.0.CO