Low expression of p27(Kip1) is associated with tumor size and poor prognosis in patients with renal cell carcinoma.
BACKGROUND
Proliferative activity in tumors depends on regulation of the cell cycle. p27(Kip1) (p27) plays a pivotal role as a negative regulator of the cell cycle. A decrease in p27 expression has been reported in many kinds of tumors, but little is known regarding p27 in patients with renal cell carcinoma (RCC).


METHODS
Expression of p27 and the related cyclins (cyclin A, cyclin E, and cyclin D1) was examined immunohistochemically in 67 patients with of clear cell RCC. The Ki-67 labeling index (MIB-1 LI) and clinicopathologic parameters related to a poor prognosis also were analyzed. To determine their prognostic significance, univariate and multivariate survival analyses were performed.


RESULTS
In tumors, there was considerable immunoreactivity for cyclin A, cyclin D1, and MIB-1, and the mean values for each were 1.08%, 16.1%, and 1.5%, respectively. Cyclin E expression was rare. The expression of p27 was correlated strongly with the expression of cyclin A (correlation coefficient, 0.432; P < 0.0004) and cyclin D1 (correlation coefficient, 0.476; P < 0.0004). Also, an inverse correlation was present between p27 expression and tumor size (P = 0.0377). In univariate analysis, the unfavorable prognostic factors were high TNM stage (P < 0.0001), large tumor size (P = 0.0016), high histologic grade (P = 0.0104), and low p27 expression (P < 0.0001). In multivariate analysis, high TNM stage (P = 0.0035) and low p27 expression (P = 0.0235) were independent prognostic factors for disease specific survival in patients with RCC.


CONCLUSIONS
The results of this study suggest that low p27 expression may be a significant and independent, unfavorable prognostic factor in patients with renal cell carcinoma.
Migita
Toshiro
T
Department of Anatomic Pathology, Kyushu University, Fukuoka, Japan.
Oda
Yoshinao
Y
Naito
Seiji
S
Tsuneyoshi
Masazumi
M
D000368:Aged; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004273:DNA, Neoplasm / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*
D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D018809:Proliferating Cell Nuclear Antigen; D025521:Tumor Suppressor Proteins; C413374:p27 antigen; D050760:Cyclin-Dependent Kinase Inhibitor p27