Fas Ligand Expression Is Correlated with Metastasis in Colorectal Carcinoma

Abstract

The Fas/Fas ligand (FasL) system is one apoptotic pathway through which malignant tumors can evade immune surveillance. While FasL is expressed in malignant tumors, Fas is conversely downregulated to escape host immune attack, resulting in tumor invasion. The aim of the current study was to find out further clinicopathological significance of FasL expression in carcinoma of the colon and rectum. FasL expression was investigated using immunohistochemical staining in 143 consecutive patients with primary colorectal carcinomas. Seventy-nine carcinomas (55.2%) expressed FasL. The incidence of lymph node and distant metastases in carcinomas expressing FasL was significantly higher than in carcinomas that did not express FasL (p = 0.031 and p = 0.0003, respectively). Although univariate analysis showed that survival in patients with carcinomas expressing FasL was significantly poorer than that in patients with carcinomas without FasL expression (p = 0.001), only Dukes’ stage was an independent prognosticator by multivariate analysis. FasL expression was found to be correlated with lymph node involvement and distant metastases in colorectal carcinoma.

Fas/FasL expression in colorectal cancer. An immunohistochemical study.

“…Similarly to our studies, many authors also found no correlations between the respective clinicohistopathological parameters, such as histological differentiation grade [14,15,[18][19][20][21], Dukes' classification [14,20], tumor histological type [20] and location [14,17,19,20], depth of infiltration [15] and the presence of local lymph node involvement or distant metastases [19]. It would be interesting to consider whether the changes in FasL protein and Fas receptor expression would be useful prognostic factors for colorectal carcinoma patients.…”

“…This may indicate FasL protein involvement in cancer progression. Nozoe et al [17] not only observed FasL correlation with metastases to lymph nodes and distant organs, but also with Dukes' classification, superficial tumor type, depth of infiltration and lymphatic permeation of the colorectal carcinoma, but not with vascular invasion. In other studies, the expression of FasL protein was found to correlate with histological type [18,19], high level of microsatellite instability (MSI-H) [18,20] and patients' survival [19].…”

FAS ligand expression in inflammatory infiltrate lymphoid cells as a prognostic marker in oral squamous cell carcinoma

“…Several authors have associated strong FASL tumor expression with lymph node metastases; examples include colorectal cancer (Nozoe et al, 2003;Pryczynicz et al, 2010), cervical adenocarcinoma (Kase et al, 2003), and oral cancer (Fang et al, 2013).…”

The role of Fas ligand and transforming growth factor β in tumor progression

“…10 In general, FasL is expressed in T lymphocytes, such as cytotoxic T cells (CTLs) in tumor-infiltrating T cells (TILs), and in natural killer (NK) cells and macrophages. Despite the fact that FasL is expressed in specific organs, including the testis and eye, 11 overexpression of FasL also is found in various tumors, including melanoma, 12 lymphoma, 13 esophageal carcinoma, 14 gastric carcinoma, 15 colon carcinoma, 16 and breast carcinoma. 17 FasL can be cleaved proteolytically to form a bioactive, soluble trimer, 18 and it can associate with lipid microvesicles that stabilize its bioactivity and prolong its biologic half-life.…”

“…56,57 Similar findings of a close correlation between apoptosis of TILs and FasL-positive tumors have been reported in patients with head and neck malignancies 58 and ovarian carcinoma. 59 Moreover, among patients with colorectal carcinoma, FasL expression levels are higher in metastatic lesions than in primary lesions, 16 and high FasL expression levels are associated with lymph node metastasis grade in breast carcinoma. 60 In addition, a high ratio of FasL to Fas can be indicative of poor prognosis in patients with ovarian carcinoma 61 and hepatic carcinoma.…”