Loss of p57KIP2 is associated with colorectal carcinogenesis.
The expression and significance of p57KIP2, an important inhibitor of the cell cycle, remain unclear during carcinogenesis and during late metastasis to lymph nodes of tumors. To detail changes of p57KIP2 during colorectal carcinogenesis and during late metastasis to lymph nodes, p57KIP2, cyclin A, cyclin B1, cyclin E, CDK2, and Ki67 were immunohistochemically investigated in 22 specimens of normal mucosa, 62 of adenomas, 17 of carcinomas in adenomas, 189 of primary carcinomas, and 23 of lymph node metastases. Situated in nuclei, p57KIP2 expression increased significantly from normal mucosa to adenomas (p=0.0068), from mild through moderate to severe dysplasia in adenomas (p=0.0132). It significantly decreased from adenomas to unpaired primary carcinomas (p=0.0112) and from peripheral adenomas to paired central carcinomas (p=0.0018), but remained unchanged when primary carcinomas metastasized to lymph nodes (p=0.3401). p57KIP2 expression was not correlated with clinicopathological indices, but the patients having tumors without p57KIP2 tended to show a poor prognosis (p=0.0674). High p57KIP2 was significantly correlated with increased cyclin A (p=0.0007), elevated cyclin B1 (p=0.0007), reduced CDK2 (p=0.0021), and increased Ki67 (p=0.0013) in adenomas. Thus, loss of p57KIP2 expression appears associated with colorectal carcinogenesis.
Li
Jia-Qing
JQ
Department of Pathology and Host-Defense, Kagawa Medical University, Kagawa 761-0793, Japan.
Wu
Fei
F
Usuki
Hisashi
H
Kubo
Akihito
A
Masaki
Tsutomu
T
Fujita
Jiro
J
Bandoh
Shuji
S
Saoo
Kousuke
K
Takeuchi
Hijiri
H
Kuriyama
Shigeki
S
Ishida
Toshihiko
T
Imaida
Katsumi
K
D000236:Adenoma / Q000378:metabolism; D000368:Aged; D042846:CDC2-CDC28 Kinases / Q000096:biosynthesis; D002277:Carcinoma / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D019925:Cyclin A / Q000096:biosynthesis; D019926:Cyclin B / Q000096:biosynthesis; D056744:Cyclin B1; D019927:Cyclin E / Q000096:biosynthesis; D051357:Cyclin-Dependent Kinase 2; D050761:Cyclin-Dependent Kinase Inhibitor p57; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D011379:Prognosis
C534699:CCNB1 protein, human; C493964:CDKN1C protein, human; D019925:Cyclin A; D019926:Cyclin B; D056744:Cyclin B1; D019927:Cyclin E; D050761:Cyclin-Dependent Kinase Inhibitor p57; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2