Immunohistochemical investigatigation of migration inhibitory factor-related protein (MRP)-14 expression in hepatocellular carcinoma

Abstract

Migration inhibitory factor-related protein (MRP)-8 and -14 belong to the S-100 protein family and are associated with myeloid cell differentiation. MRP is also expressed in some epithelia. However, there are few reports for the investigation on carcinomas. Using the monoclonal antibody 60B8 against MRP-14, we carried out the immunohistochemical evalution of MRP-14 expression in 70 cases of hepatocellular carcinoma (HCC), and examined the relation to tumor differentiation and vascular invasion. Positively stained tumor cells were detected in 32 cases, all of which belonged to grade II (7/30) or grade III (25/25) of the Edmondson-Steiner classification. In particular, the grade III HCC showed a significantly greater positive reaction. Immunopositivity in the non-carcinomatous hepatocytes and bile duct epithelia was not observed. These findings suggested that malignant hepatocytes newly express MRP-14 and that the neo-expression in differentiated HCC is related to the tumor differentiation and shows higher correlation in the poorly differentiated carcinomas. Furthermore, the cholangiocellular carcinoma and metastatic adenocarcinoma as control materials also presented a more marked immunoreactivity for MRP-14 in the poorly differentiated carcinomas, in a similar manner with the findings of the HCC. Accordingly, MRP is considered to be frequently neo-expressed in poorly differentiated carcinomas. MRP-14 expression rate in the 48 HCC cases with vascular invasion was 56%, showing no significant difference compared with non-invasive tumors.

Global Gene Expression Profiling Unveils S100A8/A9 as Candidate Markers in H-Ras-Mediated Human Breast Epithelial Cell Invasion

“…Among S100 proteins, S100A4, S100A8, and S100A9 have emerged as potential prognostic markers for poor patient survival and metastasis of a number of cancers (14,(23)(24)(25). S100A8 and S100A9 were shown to be overexpressed in gastric cancer (26,27), prostate cancer (28), breast cancer (29), lung adenocarcinomas (30), pulmonary adenocarcinoma (30), and hepatocellular carcinoma (31). Consistent with the present study, we previously showed that S100A8 and S100A9 play critical roles in the invasive phenotype of a human gastric cancer cell line, SNU484 (27).…”

Loss of myeloid-related proteins 8 and myeloid-related proteins 14 expression in human esophageal squamous cell carcinoma correlates with poor differentiation

“…It is noteworthy that MRP14 expression level has a positive correlation with the differentiation degree of carcinomas derived from glandular cells, such as hepatocellular carcinoma, cholangiocellular carcinoma and pulmonary adenocarcinoma. In poorly differentiated adenocarcinoma (AC) cases, immunoreactivity of MRP8 and MRP14 was significantly higher than that in the moderately and well differentiated AC cases [24,26] . These differences might reflect the different pathways or mechanisms that MRP8 and MRP14 were involved in tumorigenesis of different cell origin.…”

“…Previous reports have subsequently shown that the deregulation of MRP8 and/or MRP14 was associated with several common human malignancies, including carcinomas of the skin, stomach, colon, nasopharynx, lung, liver and anus, and follicular lymphoma as well [20][21][22][23][24][25][26][27][28] . Therefore, our results further suggest that reduced expression of MRP8 and MRP14 in ESCC cells, but not in normal cells, plays an important role in esophageal carcinogenesis.…”

“…Typically, MRP8 and MRP14 are known to be differentially expressed at sites of acute and chronic inflammation [16][17][18][19] . However, there is sparse information regarding the deregulation of MRP8 and/or MRP14 in several human common malignancies [20][21][22][23][24][25][26][27][28] . And little is known about the possibility of abnormal expression of MRP8 and MRP14 in ESCC.…”

Increased Myeloid-Derived Suppressor Cells in Gastric Cancer Correlate with Cancer Stage and Plasma S100A8/A9 Proinflammatory Proteins

“…S100A8/A9 are elevated in inflammatory diseases, such as rheumatoid arthritis, cystic fibrosis, and inflammatory bowel disease (23)(24)(25). In addition, they are upregulated in cancers, such as hepatocellular carcinoma (26), breast cancer (27), ovarian cancer (28), and gastric cancer (GC) (29). S100A8/A9 mediates their effects by binding to cell surface receptors, such as heparan sulfate (30), TLR4 (31), and carboxylated N-glycans expressed on RAGE (32,33), on immune cells and tumor cells.…”