Abstract
Colorectal cancer (CRC) is a major health problem in elderly people because of its high incidence and high mortality rate. Despite early screening programs, more than half of CRC patients are diagnosed at advanced stages. Fibroblast activation protein-α (FAP) expression in cancer-associated fibroblasts (CAFs) has been associated with a higher risk of metastases and poor survival. Here, we have analyzed the immunohistochemical expression of FAP in 41 adenoma-carcinoma sequences. In addition, FAP expression was analyzed individually and in combination with β-catenin (BCAT), CD44 and Cyclin-D1 expression in primary tumors and in their corresponding lymph node and liver metastases (n=294). Finally, soluble FAP (sFAP) levels in plasma from CRC patients (n=127) were also analyzed by ELISA. FAP was expressed only in CRC tissue and its expression level was found to be higher in tumors exhibiting deeper local invasion and poorer cancer cell differentiation. FAP and concomitant nuclear BCAT expression in cancer cells at the infiltrating front of primary tumors and in lymph node metastases was independently associated with 5- and 10-year cancer specific and disease-free survival. Moreover, lower sFAP levels correlated with poorer survival. These findings support the potential importance of FAP as a biomarker of CRC development and progression.
Highlights
Colorectal cancer (CRC) is one of the most common malignancies in terms of incidence and the second leading cause of cancer deaths worldwide [1]
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These authors demonstrated in vitro that medium conditioned by CRC cells, but not by adenoma cells, induces Fibroblast activation protein-α (FAP) expression in cancer-associated fibroblasts (CAFs), suggesting that FAP may be a useful diagnostic marker for early CRC invasion [23]
Summary
Colorectal cancer (CRC) is one of the most common malignancies in terms of incidence and the second leading cause of cancer deaths worldwide [1]. Cancer development and progression rely on neoplastic cells themselves, and on their interaction with other cells of the tumor microenvironment (TME), such as cancer-associated fibroblasts (CAFs) [4, 5]. These cells are the most ubiquitous elements of tumor stroma from epithelial cancers and have been proposed to be the “architects of cancer pathogenesis” [6] because of their participation in the acquisition of several hallmarks of cancer [4, 5]
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