Nestin could be a useful marker to diagnose certain types of cholangiocarcinoma, according to results of a new study published in Histopathology.

To assess the significance of nestin as a diagnostic marker in cholangiocarcinoma, a team of researchers from Japan led by Yasuni Nakanuma, MD, PhD, studied the expression pattern of the protein in the liver.

They obtained liver sections from 75 patients with combined hepatocellular-cholangiocarcinoma, 22 patients with small duct-type intrahepatic cholangiocarcinoma, 20 patients with large duct-type intrahepatic cholangiocarcinoma, and 35 patients with hepatocellular carcinoma.

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They found that nestin was expressed in 65% of patients with combined hepatocellular-cholangiocarcinoma while it was only detected in 5% of patients with large duct type intrahepatic cholangiocarcinoma and 2.9% of patients with hepatocellular carcinoma. Nestin expression was detected in a little less than half (40.9%) of patients with small duct-type intrahepatic cholangiocarcinoma.

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The researchers also found that nestin expression was partly associated with the expression of neural cell adhesion molecule and vimentin. Moreover, nestin was expressed in significantly more patients with small duct-type intrahepatic cholangiocarcinoma compared to patients with large duct-type intrahepatic cholangiocarcinoma or hepatocellular carcinoma.

In patients with combined hepatocellular-cholangiocarcinoma that were positive for nestin, the tumor size was smaller, cholangiolocellular carcinoma components were more often present, and the rate of p53 overexpression and multiple genetic alterations were higher.

Finally, the overexpression of p53 was associated with a higher histological grade and multiple genetic alterations in combined hepatocellular-cholangiocarcinoma patients who were nestin-positive.

The researchers concluded that nestin may be a useful diagnostic marker for a specific subgroup of combined hepatocellular-cholangiocarcinoma and small duct type intrahepatic cholangiocarcinoma associated with cholangiolocellular carcinoma components, p53 mutations, and multiple genetic alterations.

Nestin is a type 4 intermediate filament protein expressed in dividing cells in the nervous system as well as myogenic tissues during early development. It has also recently been proposed as a marker of angiogenesis in proliferating endothelial cells in colorectal cancer.


Sasaki M, Sato Y, Nakanuma Y. Is Nestin a diagnostic marker for combined hepatocellular-cholangiocarcinoma? Histopathology. Published online January 25, 2022. doi:10.1111/his.14622