Expression of brain-type glycogen phosphorylase is a potentially novel early biomarker in the carcinogenesis of human colorectal carcinomas.
OBJECTIVE
Our previous studies have demonstrated the significant role of brain-type glycogen phosphorylase (BGP) in the carcinogenesis of gastric carcinoma. The aims of the present study were to investigate the expression of BGP in colorectal carcinoma as well as the timing of this expression in the adenoma-carcinoma sequence (ACS), in comparison with the overexpression of p53 protein. We also sought to identify this marker in the particular colorectal mucosa bearing de novo carcinoma.


METHODS
The expression of BGP and p53 protein in colorectal carcinoma using affinity purified specific anti-human BGP antibody (Ab) and anti-p53 Ab was studied using 96 resected specimens. Further investigation to examine the timing of BGP expression in comparison with p53 overexpression was carried out using 13, 18, eight, and 16 specimens of adenoma with mild, moderate, and severe dysplasia, and carcinoma in adenoma, respectively. The BGP immunohistochemistry in whole resected human colorectal mucosa (two with carcinoma and one with ulcer) was carried out using specific anti-BGP and anti-p53 Ab.


RESULTS
The BGP visualized by immunohistochemistry was commonly present in colorectal carcinoma (83.3%). The expression of this molecule during ACS showed excellent correlation with the increased dysplasia and was found before p53 overexpression, whereas no BGP expression was seen in the normal human large intestine remote from the cancer foci. Positive staining in overtly normal-looking colonic mucosa was observed mainly around carcinomas without any adenoma component.


CONCLUSIONS
The present study is the first to localize the BGP molecule in colorectal carcinoma, adenoma, and normal mucosa. It is suggested that BGP is a novel biomarker for carcinogenesis in both the pathways of ACS and the de novo colorectal carcinoma.
Tashima
S
S
Department of Surgery II and Surgical Pathology, Kumamoto University School of Medicine, Japan.
Shimada
S
S
Yamaguchi
K
K
Tsuruta
J
J
Ogawa
M
M
D000236:Adenoma / Q000737:chemistry; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000737:chemistry / Q000175:diagnosis*; D003106:Colon / Q000201:enzymology; D003110:Colonic Neoplasms / Q000737:chemistry; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000175:diagnosis*; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000201:enzymology; D007527:Isoenzymes / Q000032:analysis; D006005:Phosphorylases / Q000032:analysis*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D014408:Biomarkers, Tumor; D007527:Isoenzymes; D016159:Tumor Suppressor Protein p53; D006005:Phosphorylases