Peptide Receptors as Targets for PET/SPECT Radiopharmaceuticals: A Breast Cancer Tissue Microarray Study
Gulisa Turashvili, Ozge Goktepe, Steven McKinney, Samuel Aparicio, Brigitte Guerin, Francois Benard. BC Cancer Research Centre, Vancouver, BC, Canada; Queen's University and Kingston General Hospital, Kingston, ON, Canada; Université de Sherbrooke, Sherbrooke, QC, Canada
Background: Peptides are short polymers of amino acids linked by peptide bonds. Peptide receptors have been shown to be overexpressed in breast cancer, and may represent targets for imaging and therapy with radiolabeled peptides. We set out to assess the frequency of peptide receptor overexpression in breast cancer, and associations with clinical and other biomarker variables.
Design: A tissue microarray was constructed from 406 cases of breast cancer, and expression of peptide receptors (BDKRB1, GRPR, NPY1R, SSTR2) was evaluated using immunohistochemistry. Median follow-up was 6.6 years. Outcome data was available in 335 cases. Clinical covariate and biomarker associations were assessed using contingency tables, and Pearson's χ2 or Fisher's exact test. Survival associations were assessed using Kaplan-Meier plots, logrank and Breslow tests, and Cox proportional hazards regression analysis.
Results: BDKRB1 was expressed in 221/291 (76%), GRPR in 219/292 (75%), NPY1R in 80/313 (26%), and SSTR2 in 300/302 (99.3%) cases. SSTR2 had no prognostic value and showed no association with any of the clinical or biomarker variables. Univariable survival analysis showed that BDKRB1, GRPR and NPY1R-negative cases had poorer overall and disease-specific survival than positive cases. Multivariable models consisting of peptide receptor scores and clinical variables showed suggestive evidence of independent prognostic value for peptide receptors. BDKRB1 and NPY1R were positively associated with ER and Bcl-2, negatively associated with histologic grade and EGFR, and associated with systemic therapy. BDKRB1 and GRPR were negatively associated with EZH2, a biomarker of poor prognosis. BDKRB1 was positively associated with NPY1R and GRPR and negatively associated with clinical T stage and EZH2. NP1YR was associated with HER2. GRPR was negatively associated with lymphovascular invasion, node status, tumor size, clinical and pathological T stage, and associated with histologic type of tumor and pathological N stage. All three peptide receptors were negatively associated with Ki-67 and showed higher expression in the luminal subtype of breast cancer.
Conclusions: Peptide receptors are expressed in a high proportion of breast cancer cases and some have prognostic value. This suggests that radiolabeled peptides targeting these receptors could be valuable agents for breast cancer diagnosis and therapy.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 26, Wednesday Morning