Prognostic Significance of p27KIP1 Protein and Ki-67 Growth Fraction in Non-small Cell Lung Cancers
2000
We
immunohistochemically examined specimens of 215 surgically resected
non-small cell lung cancers (NSCLCs) for p27 KIP1 protein
(p27) expression and the growth fraction determined by the Ki-67
labeling index (LI). The NSCLCs analyzed showed considerable
heterogeneity in both p27 and Ki-67 LIs; 25 of 207 (13%) lacked p27
expression (p27 LI < 5%), and 116 of 215 (54%) showed a high
Ki-67 LI (>30%). The p27 LI was not significantly associated with the
Ki-67 LI. A χ 2 test showed that loss of p27 expression
was inversely correlated with smoking ( P = 0.01)
and that a high Ki-67 LI was significantly associated with male gender,
squamous cell carcinoma histology, and smoking ( P < 0.0001 each). Prognostic values of p27 and Ki-67 expression were
evaluated in 109 tumors of postsurgical pathological stages I and II.
Patients with tumors lacking p27 expression survived for a
significantly shorter time than patients with tumors expressing p27
(5-year survival rates, 38% and 68%, respectively;
P = 0.02). Patients with tumors having a high Ki-67
LI survived for a significantly shorter time than patients with tumors
having a low Ki-67 LI (5-year survival rates, 48% and 78%,
respectively; P = 0.005). Multivariate analysis
showed that loss of p27 expression tended to be an unfavorable
prognostic factor ( P = 0.054), whereas a high Ki-67
LI was a significant and independent unfavorable prognostic factor
( P = 0.004). When analyzed by cell types, loss of
p27 expression was a significant and independent unfavorable prognostic
factor in squamous cell carcinomas ( P = 0.01),
whereas a high Ki-67 LI was a significant and independent unfavorable
prognostic factor in nonsquamous cell carcinomas ( P = 0.007). We further evaluated the importance of p27 expression in
clinical outcome in combination with the Ki-67 LI and ras p21 protein
(ras) expression, which we previously reported as an important
prognostic factor in NSCLCs. Patients with tumors lacking p27
expression and having a high Ki-67 LI survived for a significantly
shorter time than those with tumors expressing p27 and having a high
Ki-67 LI (5-year survival rates, 17% and 52%, respectively;
P = 0.003). Patients with p27-negative and
ras-positive tumors survived for a significantly shorter time than
those with both p27- and ras-positive tumors (5-year survival rates,
0% and 38%, respectively; P < 0.0001). These
results indicate the pivotal roles of p27 and Ki-67 expression in the
clinical outcome of NSCLCs.
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