AUTHOR=Beer Patricia , Pauli Chantal , Haberecker Martina , Grest Paula , Beebe Erin , Fuchs Daniel , Markkanen Enni , Krudewig Christiane , Nolff Mirja Christine 

TITLE=Cross-species evaluation of fibroblast activation protein alpha as potential imaging target for soft tissue sarcoma: a comparative immunohistochemical study in humans, dogs, and cats

JOURNAL=Frontiers in Oncology

VOLUME=Volume 13 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1210004

DOI=10.3389/fonc.2023.1210004

ISSN=2234-943X

ABSTRACT=Introduction: Complete surgical tumor resection is paramount in the management of soft tissue sarcoma (STS) in humans, dogs, and cats alike. Near-infrared targeted tracers for fluorescenceguided surgery (FGS) could facilitate intraoperative visualization of the tumor and improve resection accuracy. Target identification is complicated in STS due to the rarity and heterogeneity of the disease. This study aims to validate the expression of fibroblast activation protein alpha (FAP) in selected human, canine and feline STS subtypes to assess the value of FAP as a target for FGS and to validate companion animals as a translational model.Methods: Formalin fixed and paraffin embedded tissue samples from 53 canine STS (perivascular wall tumor (PWT), fibrosarcoma (cFS), STS not further specified (NOS)), 24 feline fibrosarcomas and 39 human STS (myxofibrosarcoma, undifferentiated pleomorphic sarcoma, dermatofibrosarcoma protuberans, malignant peripheral nerve sheath tumor) as well as 6 canine and 7 feline healthy controls and 10 inflamed tissue samples were immunohistochemically stained for their FAP expression. FAP labeling in tumor, peritumoral, healthy skin and inflamed tissue was quantified using a visually assessed semiquantitative expression score and digital image analysis. Target selection criteria (TASC) scoring was subsequently performed as previously described.Results: Eighty five percent (85%) of human (33/39), 76% of canine (40/53) and 92% of feline (22/24) STS showed FAP positivity in over 10 percent of the tumor cells. A high expression was determined in 53% canine (28/53), 67% feline (16/24) and 44% human STS (17/39). The average FAP labeled area of canine, feline and human STS was 31%, 33% and 42% respectively (p>0.8990). The FAP positive tumor area was larger in STS compared to healthy and peritumoral tissue (p<0.0001). TASC scores were above 18 for all feline and human STS subtypes and canine PWTs, but not for canine STS NOS and cFS.This study represents the first cross-species target evaluation of FAP for STS. Our results demonstrate that FAP expression is increased in various STS subtypes compared to noncancerous tissues across species, thereby validating dogs and cats as suitable animal models. Based on a TASC score FAP could be considered a target for FGS.