| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Molecular Oncology, Markers, Clinical Correlates |
First Department of Medicine [F. H., H. D-A., T. M., T. K., H. H., S. O., Y. K.] and Second Department of Surgery [H. K.], Hokkaido University School of Medicine; Department of Surgical Pathology, Hokkaido University Medical Hospital [M. S.]; and Department of Public Health, Sapporo Medical University [M. N.], Sapporo 060-8638, Japan
We
immunohistochemically examined specimens of 215 surgically resected
non-small cell lung cancers (NSCLCs) for p27KIP1 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 
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.
This article has been cited by other articles:
|
|
 |
|
  A. J. Buendia, J. Sanchez, C. M. Martinez, and J. A. Navarro Immunohistochemical Characterization of a Pulmonary Large-Cell Carcinoma in a Dog Vet. Pathol., July 1, 2008; 45(4): 484 - 488. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kato, S. Hayama, T. Yamabuki, N. Ishikawa, M. Miyamoto, T. Ito, E. Tsuchiya, S. Kondo, Y. Nakamura, and Y. Daigo Increased Expression of Insulin-like Growth Factor-II Messenger RNA-Binding Protein 1 Is Associated with Tumor Progression in Patients with Lung Cancer Clin. Cancer Res., January 15, 2007; 13(2): 434 - 442. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Tsubochi, N. Sato, M. Hiyama, M. Kaimori, S. Endo, Y. Sohara, and T. Imai Combined Analysis of Cyclooxygenase-2 Expression With p53 and Ki-67 in Nonsmall Cell Lung Cancer. Ann. Thorac. Surg., October 1, 2006; 82(4): 1198 - 1204. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C-Q Zhu, W Shih, C-H Ling, and M-S Tsao Immunohistochemical markers of prognosis in non-small cell lung cancer: a review and proposal for a multiphase approach to marker evaluation. J. Clin. Pathol., August 1, 2006; 59(8): 790 - 800. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Dutu, S. Michiels, P. Fouret, F. Penault-Llorca, P. Validire, S. Benhamou, E. Taranchon, L. Morat, D. Grunenwald, T. Le Chevalier, et al. Differential expression of biomarkers in lung adenocarcinoma: a comparative study between smokers and never-smokers Ann. Onc., December 1, 2005; 16(12): 1906 - 1914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Singhal, A. Vachani, D. Antin-Ozerkis, L. R. Kaiser, and S. M. Albelda Prognostic Implications of Cell Cycle, Apoptosis, and Angiogenesis Biomarkers in Non-Small Cell Lung Cancer: A Review Clin. Cancer Res., June 1, 2005; 11(11): 3974 - 3986. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-i. Fukumoto, N. Yamauchi, H. Moriguchi, Y. Hippo, A. Watanabe, J. Shibahara, H. Taniguchi, S. Ishikawa, H. Ito, S. Yamamoto, et al. Overexpression of the Aldo-Keto Reductase Family Protein AKR1B10 Is Highly Correlated with Smokers' Non-Small Cell Lung Carcinomas Clin. Cancer Res., March 1, 2005; 11(5): 1776 - 1785. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. R. Shaffer, A. Viale, R. Ishiwata, M. Leversha, S. Olgac, K. Manova, J. Satagopan, H. Scher, and A. Koff Evidence for a p27 tumor suppressive function independent of its role regulating cell proliferation in the prostate PNAS, January 4, 2005; 102(1): 210 - 215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. O-charoenrat, V. Rusch, S. G. Talbot, I. Sarkaria, A. Viale, N. Socci, I. Ngai, P. Rao, and B. Singh Casein Kinase II Alpha Subunit and C1-Inhibitor Are Independent Predictors of Outcome in Patients with Squamous Cell Carcinoma of the Lung Clin. Cancer Res., September 1, 2004; 10(17): 5792 - 5803. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. Buck, G. Glatting, and S. N. Reske Quantification of 18F-FDG Uptake in Non-Small Cell Lung Cancer: A Feasible Prognostic Marker? J. Nucl. Med., August 1, 2004; 45(8): 1274 - 1276. [Full Text] [PDF]
|
|
|
|
|
|
H. Dosaka-Akita, E. Miyoshi, O. Suzuki, T. Itoh, H. Katoh, and N. Taniguchi Expression of N-Acetylglucosaminyltransferase V Is Associated with Prognosis and Histology in Non-Small Cell Lung Cancers Clin. Cancer Res., March 1, 2004; 10(5): 1773 - 1779. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Gelen, G. O. Elpek, N. H. Aksoy, M. Ogus, and N. Keles p27 Labeling Index and Proliferation in Gastrointestinal Stromal Tumors: Correlations with Clinicopathologic Factors and Recurrence Jpn. J. Clin. Oncol., July 1, 2003; 33(7): 346 - 352. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Vesselle, J. Grierson, M. Muzi, J. M. Pugsley, R. A. Schmidt, P. Rabinowitz, L. M. Peterson, E. Vallieres, and D. E. Wood In Vivo Validation of 3'deoxy-3'-[18F]fluorothymidine ([18F]FLT) as a Proliferation Imaging Tracer in Humans: Correlation of [18F]FLT Uptake by Positron Emission Tomography with Ki-67 Immunohistochemistry and Flow Cytometry in Human Lung Tumors Clin. Cancer Res., November 1, 2002; 8(11): 3315 - 3323. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Brundage, D. Davies, and W. J. Mackillop Prognostic Factors in Non-small Cell Lung Cancer* : A Decade of Progress Chest, September 1, 2002; 122(3): 1037 - 1057. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. Buck, H. Schirrmeister, M. Hetzel, M. von der Heide, G. Halter, G. Glatting, T. Mattfeldt, F. Liewald, S. N. Reske, and B. Neumaier 3-Deoxy-3-[18F]Fluorothymidine-Positron Emission Tomography for Noninvasive Assessment of Proliferation in Pulmonary Nodules Cancer Res., June 1, 2002; 62(12): 3331 - 3334. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Lee, D. Liu, J. S. Lee, J. M. Kurie, F. R. Khuri, H. Ibarguen, R. C. Morice, G. Walsh, J. Y. Ro, A. Broxson, et al. Long-Term Impact of Smoking on Lung Epithelial Proliferation in Current and Former Smokers J Natl Cancer Inst, July 18, 2001; 93(14): 1081 - 1088. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Dosaka-Akita, F. Hommura, T. Mishina, S. Ogura, M. Shimizu, H. Katoh, and Y. Kawakami A Risk-Stratification Model of Non-Small Cell Lung Cancers Using Cyclin E, Ki-67, and ras p21: Different Roles of G1 Cyclins in Cell Proliferation and Prognosis Cancer Res., March 1, 2001; 61(6): 2500 - 2504. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
