Reduced expression of cell-cycle regulator p27(Kip1) correlates with a shortened survival in non-small cell lung cancer.
BACKGROUND
The cell cycle progression is governed by a family of cyclin-dependent kinases, which are regulated by associated cyclins and by phosphorylation. p27, a cyclin-dependent kinase inhibitor, regulates the progression from G1 into the S phase by binding and inhibiting cyclin/cdks. Although p27 mutations in human tumors are extremely rare, a reduced expression of p27 might to lead to a progression of cancer cells.


METHODS
We examined tissues that had been surgically excised from 161 unselected Japanese patients with non-small cell lung cancer, and investigated the p27 protein expression by immunohistochemistry.


RESULTS
A reduced expression of the p27 protein was found in 63 cases (39.0%). Statistical correlation was found between the reduced p27 expression and advanced stage, although no correlation was found between the level of p27 expression and the gender, T factor, N factor or histological differentiation. The 5-year survival rate in the reduced group was 35.4%, which was statistically poorer than the 63.2% rate in the normal group (P=0.0016), in patients with complete resection. In a multivariate analysis, the level of p27 expression was found to be an independent prognostic indicator.


CONCLUSIONS
We demonstrated the expression of p27 protein to be a biological prognostic indicator which can indicate the subsets of patients with either a good or poor prognosis, in patients who underwent surgical resection.
Tsukamoto
S
S
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Sugio
K
K
Sakada
T
T
Ushijima
C
C
Yamazaki
K
K
Sugimachi
K
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000032:analysis / Q000096:biosynthesis*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004791:Enzyme Inhibitors / Q000032:analysis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27