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Letter to Editor

Hepatocellular carcinoma and type 2 diabetes mellitus:

cytokeratin 8/18 expression in hepatocellular carcinoma

and glycogen-storing hepatocytes

2
Kunio Takegoshi , Eikichi Okada , Qin Su 3
1
1 Takegoshi Internal Medicine Clinic, Takaoka, Toyama 933-0014, Japan.
2 Pathological Division of Takaoka City Hospital, Takaoka, Toyama 933-8550, Japan.
3 Cell Marque, Sigma-Aldrich, Rocklin, CA 95677, USA.

Corresponding Author:
Dr. Kunio Takegoshi, Takegoshi Internal Medicine Clinic, 377-7 Nomura, Takaoka, Toyama 933-0014, Japan. E-mail: kunio@takegoshi.jp
Received: 04-07-2016; Accepted: 08-07-2016

Sir, results provide evidence for reduced to negative CK8/18
expression in glycogen-rich hepatocytes.
We have reported two patients with hepatocellular
carcinoma (HCC) and type 2 diabetes mellitus (T2DM), who The mechanism of alteration of CK8/18 expression in
showed abundant glycogen in their liver parenchyma but glycogen-rich hepatocytes has not been elucidated.
a marked reduction of glycogen content in HCC. It was Su et al. demonstrated that CK8/18 expression was
[1]
[4]
suggested that the latter was associated with appearance of reduced in excessively glycogen-storing (glycogenotic)
a Warburg type glycolysis and discussed in some detail. [2] clear hepatocytes, which also showed a relative
[1]
reduction of cytoplasmic organelles as demonstrated
Cytokeratins (CKs), the intermediate filament (IF) proteins by electron-microscopic studies. Given simple CK8/18
of epithelia, are sub-divided into type I (CK9-20) and type II expression patterns, hepatocytes are sensitive to alterations
(CK1-8) and expressed as type I/II pairs in a cell differentiation of cytokeratin architecture. Using hepatic cell culture
[3]
manner. In adult liver, hepatocyte IF comprise only CK8/18. systems, Mathew et al. reported recently that CK8/18
[3]
[5]
CK8/18 expression in normal and diseased liver has been is involved in the interplay between glucose utilization
reported, including positive expression in alcoholic and insulin signaling. The authors demonstrated that
steatohepatitis (ASH) and/or non-alcoholic steatohepatitis insulin stimulates glucose uptake, glucose-6-phosphatase
(NASH) and HCC. [3] formation, lactate release, and glycogen formation in
hepatocytes via the PI-3 kinase dependent signaling
We examined the expression of CK8/18 in the liver to pathway, and that CK8/18 IF loss makes them more efficient
investigate cytoskeletal alterations in hepatocytes, glycogen producers. This is in line with the notion that an
[5]
possibly related to changes in hepatocellular glycogen
content during hepatocarcinogenesis. Our studies insulinomimetic effect of oncogenic agents is responsible
[2]
revealed that immunoreactivity for CK8/18 was reduced for the preneoplastic hepatocellular glycogenosis, which
or frequently even negative in glycogen-rich hepatocytes is associated with a reduced or negative expression of
of background liver [Figure 1b and d], but moderately CK 8/18 in glycogenotic clear cells appearing in chronic
[4]
positive in normal hepatocytes and glycogen-poor cells human and woodchuck hepadnaviral infection. CK8/18
in HCC [Figure 1a, c, e and f]. Overexpression of CK8/18, immunohistochemistry may allow distinct recognition of
as Malory Denk bodies, which are hallmark lesions in the glycogen-rich hepatocytes as shown in glycogenotic
ASH and NASH, was not detected [Figure 1b and d]. The clear cells under various conditions. [4]
[3]
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How to cite this article: Takegoshi K, Okada E, Su Q. Hepatocellular
DOI: carcinoma and type 2 diabetes mellitus: cytokeratin 8/18 expression
10.20517/2394-5079.2016.26 in hepatocellular carcinoma and glycogen-storing hepatocytes.
Hepatoma Res 2016;2:229-30.
© 2016 Hepatoma Research | Published by OAE Publishing Inc. 229