Overexpression of peptide receptors as target for PET or SPECT radiopharmaceuticals: A tissue microarray (TMA) study

Objectives Many peptide receptors are overexpressed in breast cancer and represent potential targets for imaging and therapy with radiolabelled peptides. We aimed to assess the frequency of overexpression of peptide receptors in a large cohort of 406 breast cancer patients, and correlation with other biomarkers of prognostic or therapeutic significance.

Methods We stained tissue microarrays (TMA) by immunohistochemistry to evaluate the expression of peptide receptors (GRPR and NPY1R). Outcome data was available in 346 cases. Each tumor was scored blindly for the staining intensity. The results were analyzed using Kendall’s rank correlation coefficient between peptide receptors and other biomarkers in a multivariate analysis, as well as with survival using a parametric survival fit.

Results GRPR was expressed in 232 of 312 (74%) while NPY1R was expressed in 82 of 322 scorable tumors (25%). Both receptors were expressed in 20% of cases. Either GRPR or NPY1R were expressed in 92% of cases. NPY1R expression was associated with better survival (p = 0.0067) and correlated weakly with progesterone and estrogen receptor expression. GRPR showed a weak positive correlation with HER2 and a weak negative correlation with Ki-67. GRPR was not associated with survival on regression analysis.

Conclusions We found in a large cohort of breast cancer patients that either GRPR or NPY1R are expressed in a high proportion of cases. This suggests that radiolabelled peptide heterodimers targeting both GRPR and NPY1R could be valuable agents for breast cancer diagnosis.