Details

Autor(en) / Beteiligte

• NGUYEN, Dang M
• SAM, Kathy
• O'CONNELL, Peter
• CHANG, Jenny C
• TSIMELZON, Anna
• XIAOXIAN LI
• WONG, Helen
• MOHSIN, Syed
• CLARK, Gary M
• HILSENBECK, Susan G
• ELLEDGE, Richard M
• ALLRED, D. Craig

Titel

Molecular Heterogeneity of Inflammatory Breast Cancer: A Hyperproliferative Phenotype

Ist Teil von

• Clinical cancer research, 2006-09, Vol.12 (17), p.5047-5054

Ort / Verlag

Philadelphia, PA: American Association for Cancer Research

Erscheinungsjahr

2006

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Purpose: Inflammatory breast cancer (IBC) is associated with very poor prognosis. The aims of this study are ( a ) to prospectively identify differential gene expression patterns associated with IBC and ( b ) to confirm these pathways using tissue arrays. Experimental Design: For gene expression analysis, IBC ( n = 14) was clinically defined as rapid-onset cancer associated with erythema and skin changes, whereas non-IBC patients ( n = 20) had stage III breast cancers, and cDNA analysis was carried out using the Affymetrix (Santa Clara, CA) HG-U133A microarrays. Tissue arrays were constructed from paraffin-embedded material, and the molecular phenotype of 75 IBC was compared with results from >2,000 non-IBC. Results: Gene expression analyses indicated that IBC has higher expression of genes associated with increased metabolic rate, lipid signaling, and cell turnover relative to non-IBC tumors. Consistent with the expression analysis, IBC had statistically higher Ki-67 (93% versus 11%; P < 0.001). BAX expression, reflecting increased apoptosis and cell turnover, was significantly uniformly higher in almost all IBC (98% versus 66%; P < 0.05), whereas the expression of Bcl-2 was not significantly different. IBC tumors were more likely to be steroid hormone receptor negative (estrogen receptor, 49% versus 30%; P = 0.002; progesterone receptor, 68% versus 42%; P = 0.001). The expression of tyrosine kinases was not significantly different. E-cadherin was found to be expressed in 87% of IBC, whereas the expression p53 was not significantly different. Conclusion: This study is one of the largest molecular analyses of IBC. Both IBC and non-IBC are genetically heterogeneous with consistent differences in the molecular phenotype of IBC.