Page 37 - Read Online

Table 1: Summary of clinical and pathological data
Case 1 Case 2
Age/gender 72 years/male 73 years/male
DM type/duration 2/16 years 2/9 years
Insulin level 3.5 μU/mL 20.1 μU/mL
Body mass index (kg/m2) 20.8 22.1
Alcohol 63 g/day, 40 years No
HBsAg/cAb/sAb/HCV -/-/-/- -/+/+/-
Biopsy or resection Needle biopsy Partial resection
HCC
Size (location) 2.5 cm × 2.3 cm (S8) 1.8 cm × 1.5 cm (S8)
(3-4) mm × (3-4) mm, double (S5)
Histology Well- to moderately-differentiated adenocarcinoma Well-differentiated adenocarcinoma
PAS-positive cells diastase-PAS Small numbers negative Uneven negative
HK-II immunostaining Weak positive Weak positive
Background liver
Histology Steatohepatitis with pericellular brosis (F2-3) Liver cirrhosis, type B NASH (9 years ago)
PAS-positive cells diastase-PAS Abundant numbers negative Abundant numbers negative
HK-II immunostaining Faint positive Faint positive
DM: diabetes mellitus; HBsAg: hepatitis B surface antigen; cAb: core anti-body; sAb: surface anti-body; HCV: hepatitis C virus; HCC: hepatocellular carcinoma;
PAS: periodic acid-Schiff; HK-II: hexokinase II; NASH: non-alcoholic steatohepatitis

Figure 2: Case 1-histochemical comparison of glycogen content and hexokinase II activity in hepatocellular carcinoma tissues (a, c, e, and g) and background
liver (b, d, f, and h) (a and b: HE, ×100; c and d: periodic acid-Schiff, ×100; e and f: diastase-periodic acid-Schiff, ×100; g and h: hexokinase II, ×400)
84 of 111 (75.7%) patients with cirrhotic liver diseases, in driving the metabolic alterations toward increased
with a higher incidence in patients HCC than those aerobic glycolysis. When initial excess glycogen
[16]
without HCC. GSF were also detected in a significant stores are reduced, the storage of polysaccharides is
[11]
number of human non-cirrhotic livers (88 of 236; often largely replaced by the accumulation of neutral
[17]
[15]
33.6%). A combination of enzymatic and molecular lipids. In both of our patients, PAS-positive/D-
biological approaches has shown the striking similarities PAS-negative hepatocytes, which store glycogen
in metabolic changes in human and rat GSF, including the albeit not the excessive amounts, were detected
activation of the AKT/mammalian target of rapamycin in background livers and HCC tissues. Hepatocytes
(mTOR) and Ras/MAPK signaling cascades. [15] rich in glycogen were abundant in background liver
parenchyma but were mixed with glycogen-poor
Studies in more than 150 human explants showed cells in HCC tissues. Neither pronounced clear cells
the evidence for a characteristic sequence of cellular nor MCF were detected. Fat deposits were rare in
changes, from pre-neoplastic glycogenotic FAH via HCC tissues and background livers of both of these
various intermediate stages [mixed cell foci (MCF)] patients.
to glycogen-poor malignant phenotypes, similar
to that in animal models. [9,11] These phenotypic Changes in glycogen content frequently accompany
cellular changes are due to a metabolic switch from a shift in the expression of isoenzymes during
gluconeogenesis toward the pentose phosphate progression, e.g., from low-affinity (glucokinase/
pathway and the Warburg type of glycolysis. [9,11] In HK IV) to high affinity (HK-II) HK, [17,18] HK-II being
human HBV-associated tumorigenesis, the mTOR characteristic of Warburg type of glycolysis occurring
signaling cascade has been shown to play a crucial role in rapidly growing tumors, including HCC. [17,19]

28 Hepatoma Research | Volume 2 | Issue 1 | January 15, 2016