Expression of cell-cycle regulators, cyclin E and p21WAF1/CIP1, potential prognostic markers for gastric cancer.
OBJECTIVE
The deregulation of cyclin, cyclin-dependent kinases (CDKs) and their inhibitors could have a crucial role in the development of diverse human cancers.


METHODS
In this study, we analysed the expression of cyclin D1, cyclin E, p21WAF1/CIP1 and p27KIP1 in 84 surgically resected gastric cancers by immunohistochemistry with long-term follow-up (median 38 months). We also evaluated the relation between each cell cycle regulator and various clinicopathological findings, including age, sex, histological grade, tumour location, tumour type and stage and lymph-node metastasis.


RESULTS
Overexpression of cyclin D1 and E was detected in 21/84 (25%) and 34/84 (40.5%) patients, respectively. Normal gastric epithelium showed consistently positive immunostain for p21WAF1/CIP1 and p27KIP1 in more than 50% of nuclei. Loss of p21WAF1/CIP1 and p27KIP1 expression was noted in 45/84 (53.6%) and 44/84 (52.4%) patients, respectively. Among the various clinicopathological findings, overexpression of cyclin E was associated with lymph-node metastasis (P=0.003) and recurrence (P=0.043). Loss of p21WAF1/CIP1 expression was more frequent in diffuse type cancers (P=0.005) and was correlated with recurrence (P=0.002) and death (P=0.002). Overexpression of cyclin E and loss of p21WAF1/CIP1 expression were significantly correlated with decreased disease-free (P=0.037; P= 0.001) and overall (P=0.031; P=0.001) survival.


CONCLUSIONS
These results suggest that immunohistochemical analysis for cell cycle regulators, especially cyclin E and p21WAF1/CIP1, might be a useful prognostic indicator in gastric cancer.
Jang
S J
SJ
Department of Pathology, College of Medicine, Hanyang University KURI Hospital, Kyunggi-do, Korea.
Park
Y W
YW
Park
M H
MH
Lee
J D
JD
Lee
Y Y
YY
Jung
T J
TJ
Kim
I S
IS
Choi
I Y
IY
Ki
M
M
Choi
B Y
BY
Ahn
M J
MJ
D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D019927:Cyclin E / Q000032:analysis*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000473:pathology*; D016019:Survival Analysis
D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins