Expression of thymidylate synthase in human gastric and colorectal adenocarcinomas is upregulated by p16/INK4.
OBJECTIVE
We observed the relationship between the expression of thymidylate synthase protein (pTS) and cell cycle regulators in gastric and colorectal adenocarcinoma tissues.


METHODS
This study included 80 gastric and 50 colorectal adenocarcinomas. Immunohistochemical staining was performed using a polyclonal antibody to recombinant human pTS, and monoclonal antibodies to p53, p21/WAF1CIP1, p16/INK4, cyclin D1 and pRB. Each staining was quantified using computerized image analysis on a CAS 200 system. We selected the mean expression values as the cutoff values to distinguish between high and low expression of these substances.


RESULTS
There was no relationship between pTS expression and p21/WAF1CIP1, cyclin D1, or pRB expression in gastric and colorectal carcinomas. In both gastric and colorectal carcinomas, the pTS expression was significantly low in the high p16/INK4 expression subgroup compared with the low p16/INK4 expression subgroup (P < 0.05). Further, the pTS expression was significantly high in the high p53 expression subgroup compared with the low p53 expression subgroup in colorectal adenocarcinomas (P < 0.05).


CONCLUSIONS
pTS expression regulation in human gastric and colorectal adenocarcinomas in complex, and upregulated by p16/INK4.
Omura
K
K
Department of Surgery I, Kanazawa University School of Medicine Faculty of Medicine, Japan. omura@med.kanazawa-u.ac.jp
Uno
Y
Y
Kawakami
K
K
Kanehira
E
E
Tawaraya
K
K
Tsukayama
M
M
Hiranuma
C
C
Watanabe
Y
Y
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D013940:Thymidylate Synthase / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
D018797:Cell Cycle Proteins; D013940:Thymidylate Synthase