High Expression of DCN and HSP90B1 in Breast Cancer Is Associated with LN and Distant Metastases and Decreased Overall Survival.
Juan C Moreno, Danh Tran-Thanh, Tom Cawthorn, Lindsay Jacks, Suzanne Ackloo, Pei Hong Zhu, Moyez Dharsee, Girish Sardana, Jian Chen, Kenneth R Evans, David McCready, Wey L Leong, Susan J Done. Campbell Family Institute for Breast Cancer Research, Toronto, ON, Canada; University Health Network, Toronto, ON, Canada; University of Toronto, ON, Canada; Ontario Cancer Biomarker Network, Toronto, Canada
Background: Patients with local breast cancer have a better 5 year overall survival (OS) (98%) than patients with lymph node (LN) (83.6%) or distant metastasis (23.4%). Biomarkers that improve patient classification before metastases are evident have clinical utility. During a biomarker discovery study our laboratory found a correlation between high expression of Decorin (DCN) and HSP90B1 and LN metastasis.
Decorin is a key modulator of the tumour microenvironment, mainly in an antioncogenic role, but also increases migration of osteosarcoma cells and is highly expressed in endothelial cells undergoing angiogenesis. HSP90B1 excerpts a pro-oncogenic role that facilitates cell survival decreasing apoptosis and stimulating cell proliferation, transcription and migration. To determine the clinical significance of high expression of DCN and HSP90B1 in tumour tissues, we examined the expression of both proteins in 990 different breast cancers and correlated that expression with clinical parameters.
Design: Stage 1 and 2 prognostic human breast cancer tissue microarrays annotated with clinicopathological data, including disease-free survival (DFS) and OS, were purchased from the National Cancer Institute. Immunohistochemical scores were determined using a semi-quantitative scoring system under light microscopy and image analysis software. DCN staining was evaluated separately in the stroma (DS) and the malignant epithelium (DE). HSP90B1 was scored in the malignant epithelium only (HE).
Results: High expression of DE was associated with LN metastasis p<0.0001, higher number of positive LNs p<0.0001 and worse OS p: 0.01. High expression of DS was not associated with LN status. High HSP90B1 expression was associated with presence of distant metastasis p<0.0002, worse OS p<0.0001 and worse DFS p<0.0001.
Conclusions: These results suggest that high expression of DCN in invasive breast cancer cells could be used as a prognostic marker for OS and LN metastasis. In addition, high expression of HSP90B1 appear to be a prognostic marker for OS and distant metastasis and a predictive marker for hormone therapy benefit even in patients with negative hormone receptor status.
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 7, Wednesday Afternoon