Abstract
To explore the expression of lamininγ2 in extrahepatic cholangiocarcinoma (EHCC) tissues and its influence on tumor invasion and metastasis. Paraffin embedding samples of cancer, para-cancer, lymph node metastatic and hepatic metastatic tissues from 79 patients undergoing EHCC resection were collected. Expression of lamininγ2 was detected by immunohistochemistry and its relationship with clinical pathological characteristics and the prognosis of EHCC patients were analyzed. Lamininγ2 showed negative staining in para-cancer tissues, but demonstrated a 51.9% (41/79) positive expression rate in extracellular matrix (ECM) or cytoplasm of EHCC tissues. In lymph node metastatic and distant metastatic nidi, expression of lamininγ2 was significantly higher than in the primary nidi (χ2=7.4173, P=0.0065; χ2=4.0077, P=0.0453). The expression was in obvious association with lymph node metastasis (P<0.01), but had no relevance with age, gender, tumor location, tumor stage, differentiation and distant metastasis in ECM (P>0.05), whereas it was in marked connection with lymph node and distant metastasis (P<0.05 or P<0.01), but had no relationship with age, gender, tumor location, tumor stage and differentiation in cytoplasm (P>0.05). However, the median survival time and median recurrent period of patients with positive expression of lamininγ2 in both cytoplasm and ECM of tumor cells, only in ECM and only in cytoplasm, were evidently lower than with negative expression of lamininγ2 in RCM and cytoplasm (P<0.05 or P<0.01). Further Cox regression analysis showed that the positive expression of lamininγ2 and the tumor differentiation were independent risk factors influencing the prognosis of EHCC patients. Abnormal expression of lamininγ2 may be closely associated with invasion and metastasis of tumor cells, and thus a potential molecular marker for prognosis of EHCC patients.
Highlights
Extrahepatic cholangiocarcinoma (EHCC), which is a kind of malignant tumor derived from the extrahepatic biliary epithelial cells with high malignant severity and recessive attack, is generally treated with surgeries (Pattanathien et al, 2013; Huai et al, 2014)
The expression was in obvious association with lymph node metastasis (P0.05), whereas it was in marked connection with lymph node and distant metastasis (P
Expression of Lamininγ2 in primary nidi, metastatic nidi and para-cancer tissues In extrahepatic cholangiocarcinoma (EHCC) tissues, Lamininγ2 expressed in ECM and cytoplasm, with positive rate being 51.90% (41/79), in which 39.24% (31/79) expressed in ECM, 32.91% (26/79) in cytoplasm and 20.25% (16/79) in both ECM and cytoplasm
Summary
Extrahepatic cholangiocarcinoma (EHCC), which is a kind of malignant tumor derived from the extrahepatic biliary epithelial cells with high malignant severity and recessive attack, is generally treated with surgeries (Pattanathien et al, 2013; Huai et al, 2014). Laminin332, as a macromolecular glycoprotein, is widely distributed in epithelial cells. It plays an important biological function in the metastasis, proliferation, growth and differentiation of cells by combing with receptors to mediate the adhesion between cells and basilar membrane (Kamoshida, et al, 2014). Studies demonstrated that the abnormal distribution of Laminin332 might be in close association with the malignant transformation of epithelial cells as well as the invasion and metastasis of tumors (Kariya et al, 2012; Kim et al, 2012). As a special part of Laminin332, is secreted in monomeric form, which has no expression in normal intrahepatic biliary epithelial cells and the basilar membrane of biliary epithelial tissues, but expresses highly in the cytoplasm of cholangiocarcinoma cells and extracellular matrix (ECM) (Liu et al, 2014)
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