Fetal-type Glycogen Phosphorylase Expression in IntestinalMetaplasia as a Predictor of the Development of Gastric Cancer
2018
Glycogen phosphorylase (GP; EC 2.4.1.1) plays a central role in the mobilization
of carbohydrate reserves in a wide variety of organs and tissues. There are three
major isoforms of mammalian GP; i.e., the muscle, liver, and brain isoforms. The
physiological roles of muscle and liver GP are to provide fuel for energy production
(to produce the energy required for muscle contraction) and to ensure a constant
supply of glucose to extra hepatic tissues, respectively. However, the physiological
role of brain GP (BGP) is poorly understood. It has been demonstrated that BGP is
the major isoform of GP found in fetal tissue and tumor tissue, and BGP is identical
to fetal-type GF (FGP).
We have demonstrated that the significant enzymatic activity of FGP in the gastric
carcinoma and proliferating cells of particular Intestinal Metaplasia (IM). We
studied 136 specimens with gastric carcinoma and the adjacent IM using specific
anti-FGP antibody. FGP was expressed in 80% of the intestinal type and 19% of
the diffuse type of carcinoma and in 88% and 42% in the generative zone of IM
adjacent to each type of cancer foci, respectively. The proportion of the positivity
of FGP expression in the cancer and IM was significantly greater in intestinal type
carcinoma than in diffuse type. In addition, according to the proliferating cell
nuclear antigen labeling index analysis, IM with FGP expression (FGP-IM) were
significantly higher in a proliferating state than in IM without FGP, and some of
them were co-expressed accumulated p53 in the generative cells. These data
indicate that FGP could be one of the fetal biomarkers and FGP-IM could be a
premalignant lesion of intestinal type adenocarcinoma.
We conducted another study to investigate the incidence of FGP-IM in gastric
biopsy specimens and to identify FGP-IM as a predictor of the coexistence of
accessory carcinoma and/or metachronous carcinoma. Eight endoscopic biopsy
specimens of methylene blue-positive mucosa of the stomach were obtained from
the patients with multiple gastric carcinomas (n=14), a single carcinoma (n=25)
and atrophic gastritis (n=20), examined the incidence of FGP-IM. FGP positivity
was 93.3% in the multiple carcinomas and 80.0% in the single carcinomas.
The incidences of FGP-IM in the stomachs with multiple carcinomas, single
carcinoma and atrophic gastritis were 83.2 ± 22.8%, 36.5 ± 41.3% and 7.1 ± 18.0%,
respectively. The incidence of FGP-IM was significantly higher in the stomachs
with multiple carcinomas than in those with a single carcinoma or atrophic
gastritis. It is suggested that the frequent appearance of FGP-IM reflects the high
potential of carcinogenesis of intestinal type gastric carcinoma and FGP-IM could
be a predictive indicator of metachronous gastric carcinoma. Recently, there are
increasing opportunities where endoscopic and laparoscopic local treatments are
applied for the early gastric carcinoma, therefore, it is significantly important to
identify the high-risk group of metachronous recurrence of gastric carcinoma.
FGP could serve as a potential predictor of the risk of the development of multiple
and/or metachronous carcinomas. It might be possible to follow-up new lesions
using this method, and follow-up studies would provide better information on
whether FGP-IM positivity is a good predictor of metachronous recurrence after
local treatment for gastric cancer.
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