p107 Expression in colorectal tumours rises during carcinogenesis and falls during invasion.
p107 Links to cyclin A/CDK2 (cyclin-dependent kinase 2) and cyclin E/CDK2 that are important cell cycle regulators. However, p107 expression remains unclear in almost all kinds of human solid tumours. To clarify the expression of p107 in colorectal tumours, 22 normal mucosae, 9 hyperplastic polyps, 60 adenomas, 198 primary carcinomas, 21 lymph-nodal metastases, and 10 hepatic metastases were immunohistochemically stained for p107, cyclin A, cyclin E, CDK2 and Ki67. Results were measured using labelling indices (LIs). p107 LIs surpassed the highest value in normal tissues in six of nine hyperplastic polyps, 54 of 60 adenomas, 144 of 198 primary cancers, 13 of 21 nodal foci and three of 10 hepatic foci. p107 LIs also apparently rose from normal through hyperplasia and adenoma to early carcinoma. However, they declined in liver-metastatic foci, and in primary cancers showing large size, mucinous type, venous invasion, lymphatic invasion, poorly differentiated type, deep invasion, lymph-nodal metastasis, hepatic metastasis or advanced stage. Low p107 LIs were also linked to a poor survival, particularly in stage-III patients. As the p107 LI gradually rose, the CDK2 (in primary cancers only), cyclin A, cyclin E and Ki67 LIs were elevated concurrently-in both adenomas and primary cancers. Thus, in colorectal tumours, p107 expression rises abnormally and gradually during carcinogenesis and then falls during invasion, and thereby probably perturbs the cell-cycle control and promotes carcinogenesis and invasion. Clinically, reduced p107 may indicate a poorer prognosis.
Third Department of Internal Medicine, Kagawa Medical University, 1750-1, Miki-cho, Kita-gun, 761-0793, Kagawa, Japan
F
F
Wu
J Q
JQ
Li
H
H
Miki
M
M
Nishioka
J
J
Fujita
M
M
Ohmori
K
K
Imaida
S
S
Kuriyama
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D042846:CDC2-CDC28 Kinases; D015179:Colorectal Neoplasms / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008113:Liver Neoplasms / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D011379:Prognosis; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D050720:Retinoblastoma-Like Protein p107
D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C493844:RBL1 protein, human; D050720:Retinoblastoma-Like Protein p107; D011494:Protein Kinases; C102333:histone H1 kinase; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases