Expression of endothelin-1, endothelin-A, and endothelin-B receptor in human breast cancer and correlation with long-term follow-up.

Abstract

PURPOSE:

Endothelin-1 (ET-1) is overexpressed in breast carcinomas and stimulates tumor cell growth in an autocrine and paracrine fashion via its receptors, ET(A)R and ET(B)R. In this study, we evaluated the expression of ET-1 and ET receptors in breast carcinomas and determined its clinical and prognostic significance.

EXPERIMENTAL DESIGN:

We analyzed expression of ET-1, ET(A)R, and ET(B)R in 176 breast carcinomas using a semiquantitative immunohistochemical approach. Statistical analysis of clinicopathological variables such as pT stage, pN stage, hormone receptor status, Her-2/neu amplification, histological grade, and long-term follow-up data were performed.

RESULTS:

We observed a moderate to strong cytoplasmic staining for ET-1 in 69 (43.1%), for ET(A)R in 74 (46.5%), and for ET(B)R in 86 (53.4%) cases of primary breast cancer. A correlation was found between increased ET-1 expression and its receptors with several clinicopathological parameters that characterize aggressive types of breast cancer, with the exception of increased ET(A)R and ET(B)R expression with positive estrogen receptor status. Elevated expression of ET-1, ET(A)R, and ET(B)R was more common in breast carcinomas of patients with lower disease-free survival time and overall survival. In addition, a statistically significant correlation was observed between ET(A)R expression and reduced disease-free survival time (P = 0.041). Interestingly, the prognostic impact of ET(A)R expression was shown to be more pronounced in the subgroup of patients with a putative favorable prognosis according to classic prognostic factors.

CONCLUSIONS:

Therefore, analysis of ET(A)R expression may improve the prediction of relapse and death and facilitate an individually based risk-directed adjuvant therapy in breast cancer patients.

• Authors: Pia Wülfing, Raihanatou Diallo, Christian Kersting, Christian Wülfing, Christopher Poremba, Achim Rody, Robert R Greb, Werner Böcker, Ludwig Kiesel
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 9 Issue 11 Pg. 4125-31 (Sep 15 2003) ISSN: 1078-0432 [Print] United States
• PMID: 14519635 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Endothelin-1
• Receptor, Endothelin A
• Receptor, Endothelin B

Topics

• Breast Neoplasms (mortality, pathology)
• Disease-Free Survival
• Endothelin-1 (analysis)
• Female
• Humans
• Immunohistochemistry
• Lymphatic Metastasis
• Multivariate Analysis
• Neoplasm Metastasis
• Neoplasm Staging
• Receptor, Endothelin A (analysis)
• Receptor, Endothelin B (analysis)
• Reproducibility of Results
• Survival Analysis
• Time Factors