Tumor Progression from a Fibroblast Activation Protein Perspective: Novel Diagnostic and Therapeutic Scenarios for Colorectal Cancer
Martina Rossetti,
Stefano Stanca,
Rossella Del Frate,
Francesco Bartoli,
Andrea Marciano,
Enrica Esposito,
Alessandra Fantoni,
Anna Paola Erba,
Piero Vincenzo Lippolis,
Pinuccia Faviana
Affiliations
Martina Rossetti
Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, 56126 Pisa, Italy
Stefano Stanca
Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, 56126 Pisa, Italy
Rossella Del Frate
Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, 56126 Pisa, Italy
Francesco Bartoli
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
Andrea Marciano
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
Enrica Esposito
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
Alessandra Fantoni
Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, 56126 Pisa, Italy
Anna Paola Erba
Department of Medicine and Surgery, University of Milan Bicocca and Nuclear Medicine Unit ASST Ospedale Papa Giovanni XXIII Bergamo, 24127 Bergamo, Italy
Piero Vincenzo Lippolis
Department of General Surgery, University Hospital of Pisa, 56124 Pisa, Italy
Pinuccia Faviana
Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, 56126 Pisa, Italy
In 2020, the Global Cancer Observatory estimated the incidence of colorectal cancer (CRC) at around 10.7% coupled with a mortality rate of 9.5%. The explanation for these values lies in the tumor microenvironment consisting of the extracellular matrix and cancer-associated fibroblasts (CAFs). Fibroblast activation protein (FAP) offers a promising target for cancer therapy since its functions contribute to tumor progression. Immunohistochemistry examination of FAP, fibronectin ED-B, and CXCR4 in primary tumors and their respective synchronous and/or metachronous metastases along with semiquantitative analysis have been carried out on histological samples of 50 patients diagnosed with metastatic CRC. The intensity of FAP, articulated by both “Intensity %” and “Intensity score”, is lower in the first metastasis compared to the primary tumor with a statistically significant correlation. No significant correlations have been observed regarding fibronectin ED-B and CXCR4. Tumors that produce FAP have an ambivalent relationship with this protein. At first, they exploit FAP, but later they reduce its expressiveness. Although our study has not directly included FAP-Inhibitor (FAPI) PET/CT, the considerable expression of FAP reveals its potential as a diagnostic and therapeutic tool worthy of further investigation. This dynamic relationship between cancer and FAP has substantial diagnostic and therapeutic implications.
