The multifaceted expression of the gastrin releasing peptide receptor in prostate cancer

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Abstract Gastrin releasing peptide receptor (GRPR) gained interest for targeted radionuclide therapy (TRT) of prostate cancer (PCa). However, its expression in advanced disease remains understudied. We correlated clinical, biological, molecular and pathological characteristics, with GRPR expression in PCa patient-derived xenograft (PDX) models, and compared it with prostate specific membrane antigen (PSMA) expression. GRPR expression was studied on tissue microarrays of 107 PDXs using immunohistochemistry. Seventy-six samples were GRPR positive. There were no differences in GRPR expression between primary and metastatic lesions, and androgen-naïve, androgen sensitive and castration resistant samples. High GRPR expression was frequent in androgen receptor (AR) positive tumors, high PSMA-expressing tumors, tumors without phosphatase and tensin homolog (PTEN) loss, and vimentin negative tumors. AR-positivity was the most important predictor of high GRPR expression. In PSMA negative tumors, GRPR expression was high in chromogranin positive tumors, tumors without PTEN loss, in absence of retinoblastoma1-gene mutation, and high vimentin-expressing tumors. Among the neuroendocrine PCa’s (NEPC), 14/20 were GRPR and 3/20 were PSMA positive. All PSMA positive tumors were GRPR positive. Among metastatic NEPC samples, 9/10 and 1/10 were GRPR and PSMA positive, respectively. Based on the aforementioned, we conclude that GRPR is a relevant target for advanced PCa. Moreover, the selective GRPR expression in NEPC opens new avenues for GRPR-TRT.

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