Abstract

IntroductionFibroblast activation protein (FAP) has been recently presented as new imaging target for malignant diseases and offers high contrast to surrounding normal tissue. FAP tracer uptake has been reported in various tumor entities. The aim of this study was to compare FAP and Prostate-specific membrane antigen (PSMA) expression in primary prostate cancer employing histological analyses and PET imaging in two small patient collectives.MethodsTwo independent small patient collectives were included in this study. For cohort A, data of 5 prostate cancer patients and 3 patients with benign prostate hyperplasia were included. Patients with prostate cancer were initially referred for PSMA PET staging. Radical prostatectomy was performed in all patients and prostate specimen of patients and biopsies of healthy controls were available for further evaluation. Histological workup included HE and immunohistochemistry using PSMA Ab, FAP Ab. Cohort B consists of 6 Patients with diagnosed mCRPC and available PSMA as well as FAP PET.ResultsPatients with proven prostate cancer infiltration exhibited strong positivity for PSMA in both primary tumors and lymph node metastases while stainings for FAP were found positive in some cases, but not all (2/5). Controls with BPH presented moderate PSMA staining and in one case also with a positive FAP staining (1/3). PET imaging with FAP seemed to result in more precise results in case of low PSMA expression than PSMA-PET.ConclusionsWhile PSMA staining intensity is a valid indicator of prostate cancer in both primary tumor and lymph node metastases, the expression of FAP seems to be heterogeneous but not necessarily linked to cancer-associated fibroblasts. It is also present in inflammation-associated myofibroblasts. Therefore, its ultimate role in prostate cancer diagnosis remains a subject of discussion.

Highlights

  • Fibroblast activation protein (FAP) has been recently presented as new imaging target for malignant diseases and offers high contrast to surrounding normal tissue

  • In this study we aimed to investigate the usefulness of FAP as a target for immunohistochemistry (IHC), imaging and subsequent theranostic approaches in prostate cancer besides Prostate-specific membrane antigen (PSMA)

  • Patient A5 was found positive for PSMA in both prostate and LN, but negative for FAP in both tissues (Fig. 1)

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Summary

Introduction

Fibroblast activation protein (FAP) has been recently presented as new imaging target for malignant diseases and offers high contrast to surrounding normal tissue. Conclusions While PSMA staining intensity is a valid indicator of prostate cancer in both primary tumor and lymph node metastases, the expression of FAP seems to be heterogeneous but not necessarily linked to cancer-associated fibroblasts. FAP overexpression leads to a higher risk of tumor invasion, lymph node metastasis and to decreased overall survival (OS) [2] and has been shown to be expressed in various cancers including prostate cancer, as well as chronic inflammatory diseases with fibrotic changes [3]. In terms of prostate cancer, the role of FAP has not been fully investigated yethowever it seems to have potentially beneficial features for diagnosis through imaging in prostate-specific membrane antigen (PSMA)-negative or -low disease

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