Molecular classification of primary breast tumors possessing distinct prognostic properties.

The natural progression of breast cancer differs greatly between patients; the precise prediction of this disease course will improve the efficacy of therapeutics. Gene expression profiling may elucidate the undiscovered biological variations between seemingly similar cancers, leading to a new cancer classification system valuable in accurate diagnosis. The expression levels of 2412 genes, derived from 98 cancer samples, were precisely recorded by a high throughput RT-PCR technique, adapter-tagged competitive PCR. Subsequent cluster analysis revealed a molecular profile, correlating with estrogen receptor levels and the presence of lymph node metastases. We analyzed 301 cancer samples for the expression patterns of 21 genes critical in this categorization. The classification of the samples into three major groups was verified utilizing principal component analysis. This molecular classification system correlated significantly with early recurrence, independent of lymph node status. This malignant potential is associated with the expression levels of a group of genes, which comprise a set of candidates potentially useful in diagnostic prediction. These genes and the associated control mechanisms may also be effective therapeutic targets.

[1]  Santa Jeremy Ono,et al.  Human X-box-binding protein 1 is required for the transcription of a subset of human class II major histocompatibility genes and forms a heterodimer with c-fos. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[2]  J. Coindre,et al.  Prognostic significance of breast cancer axillary lymph node micrometastases assessed by two special techniques: reevaluation with longer follow-up. , 1992, British Journal of Cancer.

[3]  K Matsubara,et al.  Gene expression in mouse cerebellum during its development. , 2000, Gene.

[4]  N. Sampas,et al.  Molecular classification of cutaneous malignant melanoma by gene expression profiling , 2000, Nature.

[5]  F. Bertucci,et al.  Gene expression profiling of primary breast carcinomas using arrays of candidate genes. , 2000, Human molecular genetics.

[6]  H. Harman Modern factor analysis , 1961 .

[7]  J. Tjandra,et al.  Detection and significance of occult metastases in node‐negative breast cancer , 1993, The British journal of surgery.

[8]  M. Macleod,et al.  Effects of estrogen on global gene expression: identification of novel targets of estrogen action. , 2000, Cancer research.

[9]  D.,et al.  Regression Models and Life-Tables , 2022 .

[10]  D. Botstein,et al.  Cluster analysis and display of genome-wide expression patterns. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[11]  Ash A. Alizadeh,et al.  Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling , 2000, Nature.

[12]  Kikuya Kato,et al.  Adaptor-tagged competitive PCR: a novel method for measuring relative gene expression. , 1997, Nucleic acids research.

[13]  R. Wooster,et al.  Cancer classification with DNA microarrays is less more? , 2000, Trends in genetics : TIG.

[14]  K Matsubara,et al.  Gene expression profiling of mouse postnatal cerebellar development. , 2000, Physiological genomics.

[15]  N. Tommerup,et al.  Human rab11a: transcription, chromosome mapping and effect on the expression levels of host GTP‐binding proteins , 1998, FEBS letters.

[16]  P. Lavagnini,et al.  Reverse transcriptase-polymerase chain reaction for prostate-specific antigen may be a prognostic indicator in breast cancer. , 1996, British Journal of Cancer.

[17]  E. Hovig,et al.  Identification of a novel cytokeratin 19 pseudogene that may interfere with reverse transcriptase‐polymerase chain reaction assays used to detect micrometastatic tumor cells , 1999, International journal of cancer.

[18]  W. Sly,et al.  Purification and kinetic analysis of recombinant CA XII, a membrane carbonic anhydrase overexpressed in certain cancers. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[19]  J. Mesirov,et al.  Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. , 1999, Science.

[20]  P. Kantoff,et al.  Two differentially expressed genes in normal human prostate tissue and in carcinoma. , 1996, Cancer research.

[21]  T. Hill,et al.  Different proportions of various prostate‐specific antigen (PSA) and human kallikrein 2 (hK2) forms are present in noninduced and androgen‐induced LNCaP cells , 2000, The Prostate.

[22]  Christian A. Rees,et al.  Molecular portraits of human breast tumours , 2000, Nature.

[23]  J. Hoying,et al.  HER2/neu over‐expression induces endothelial cell retraction , 2001, International journal of cancer.

[24]  P. Watson,et al.  The potential role for prolactin-inducible protein (PIP) as a marker of human breast cancer micrometastasis , 1999, British Journal of Cancer.

[25]  L. Liotta,et al.  Laser-capture microdissection: opening the microscopic frontier to molecular analysis. , 1998, Trends in genetics : TIG.