6d–f). In addition, significantly increased integrin expression was also detected under subconfluent culture conditions (Fig. 6d–f). IN THE PRESENT study, little or no expression of the β6, β4 and α3 integrins was immunohistochemically shown in CoCC, whereas high expression levels of these integrins were evident in CCC. Integrin mRNA levels were high in most of the CCC cell lines, but they were almost undetectable in most Selleckchem Y27632 of the HCC cell lines, as previously reported for integrin β6.[21] These

results indicated that the expression levels of these integrins, including both the injury-induced type integrin β6 and bile duct-specific integrins β4 and α3 are downregulated in CoCC in contrast to their overexpression in CCC. Furthermore, immunostaining for integrins, PI3K inhibitor particularly integrin β4, revealed high specificity and a highly positive predictive value with regard to differentiation between CoCC and CCC, indicating a diagnostic value of the present immunohistochemical findings. An algorithm for the differential diagnosis of CoCC, CCC and HCC using immunohistochemistry is shown in Figure 7. The high integrin expression frequently encountered in CCC was not related to the gross type and histological differentiation grade of the tumor, even though the peripheral mass-forming type of CCC has been shown to have histological features similar to CoCC.

The aberrant expression of the β6 and β4 integrins, with three different expression patterns, cytoplasmic, cell membrane

上海皓元 and basal lamina types, in CCC was also demonstrated in the present study, though its significance remains to be clarified. The expression of these integrins in CoCC resembled the expression of integrins in HCC. In addition, the CoCC samples in the present study were significantly associated with chronic viral hepatitis and liver cirrhosis, which is well known in HCC. CoCC exhibits a biliary phenotype with CK7 and CK19 positivity, as does CCC, in addition to a microtubular structure resembling cholangioles or canals of Hering, but it also has been shown to have some intermediate features with a trabecular structure and AFP positivity similar to HCC. In addition, CoCC has been reported to show hepatic stem cell/progenitor cell features that are suggestive of hepatic progenitor cell origin.[4, 30, 31] The low expression of integrins in CoCC, similar to that in HCC in the present study, may be associated with intermediate phenotypes of CoCC cells that are possibly derived from hepatic progenitor cells. In fact, the downregulation of integrin expression in CoCC components and HCC components in contrast to the enhanced expression in CCC components was also observed in classical CHC, the histogenesis of which has been suggested to be associated with hepatic progenitor cells.