| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Molecular Oncology, Markers, Clinical Correlates |
III Medical Department, Pulmonary Division, University Hospital, D-55101 Mainz, Germany [P. M., M. B., K. M. B., B. F., R. B.]; Institutes of Toxicology [F. O., J. G. H.], Medical Biostatistics, Epidemiology and Informatics [A. F.], and Pathology [F. B.], Mainz University, 55101 Mainz, Germany; and Ludwig Institute for Cancer Research, Biomedical Center, 75124 Uppsala, Sweden [L. R., A. B.]
Purpose: The tyrosine-kinase receptor c-kit and its ligand stem cell factor are coexpressed in many small cell lung cancer (SCLC) cell lines, leading to the hypothesis that this coexpression constitutes an autocrine growth loop. To further evaluate the frequency and pathogenic relevance of c-kit expression, tumor tissue together with the corresponding clinical data of SCLC patients was analyzed.
Experimental Design: Tumor tissue of 102 consecutive SCLC cancer patients was analyzed immunohistochemically using an affinity-purified polyclonal c-kit antibody. Immunostaining data were correlated with survival and other relevant clinical parameters.
Results: A positive c-kit expression was observed in 37% of patients. c-kit expression was associated with decreased survival in the likelihood-ratio-forward selection model of the Cox regression including clinically relevant risk factors (c-kit expression, age, gender, stage, tumor stage, node stage, metastasis stage, weight loss, performance status, response to chemotherapy, lactate dehydrogenase, neuronspecific enolase, hemoglobin). Only c-kit expression [hazard ratio, 2.00; confidence interval (CI), 1.17–3.41; P = 0.012], response to chemotherapy (hazard ratio, 4.49; CI, 2.36–8.55; P < 0.001), and tumor stage (hazard ratio, 2.11; CI, 1.18–3.74; P = 0.008) were explanatory prognostic factors. These factors and all possible interactions between them were further analyzed in a second Cox regression model. As expected, response to chemotherapy had the highest impact on survival (hazard ratio, 3.06; CI, 1.69–5.54; P < 0.001). In patients with extensive disease, minor response to chemotherapy, and positive c-kit expression, the risk to die increased to 8.4 (hazard ratio, 2.74; CI, 1.52–4.91; P = 0.002). In a Kaplan-Meier analysis median survival of patients with minor response to chemotherapy and extensive stage was 288 days (CI, 255–321 days) when c-kit expression was negative compared with only 71 days (CI, 0–237 days) for c-kit-positive patients (log rank test: P = 0.003).
Conclusions: c-kit represents a new prognostic factor in SCLC. c-kit expression is of particular clinical relevance in patients with advanced disease and poor response to chemotherapy. Given the very limited therapeutic options and unfavorable prognosis of these patients, clinical studies aimed at targeting c-kit (e.g., STI571) are clearly warranted.
This article has been cited by other articles:
|
|
 |
|
  N. Rehfeld, H. Geddert, A. Atamna, H. E. Gabbert, U. Steidl, R. Fenk, R. Kronenwett, R. Haas, and U.-P. Rohr Coexpression of Fragile Histidine Triad and c-kit Is Relevant for Prediction of Survival in Patients with Small Cell Lung Cancer. Cancer Epidemiol. Biomarkers Prev., November 1, 2006; 15(11): 2232 - 2238. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Potapova, A. D. Laird, M. A. Nannini, A. Barone, G. Li, K. G. Moss, J. M. Cherrington, and D. B. Mendel Contribution of individual targets to the antitumor efficacy of the multitargeted receptor tyrosine kinase inhibitor SU11248 Mol. Cancer Ther., May 1, 2006; 5(5): 1280 - 1289. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Tsurutani, K. A. West, J. Sayyah, J. J. Gills, and P. A. Dennis Inhibition of the Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin Pathway but not the MEK/ERK Pathway Attenuates Laminin-Mediated Small Cell Lung Cancer Cellular Survival and Resistance to Imatinib Mesylate or Chemotherapy Cancer Res., September 15, 2005; 65(18): 8423 - 8432. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Lee, D. Lopes de Menezes, J. Vora, A. Harris, H. Ye, L. Nordahl, E. Garrett, E. Samara, S. L. Aukerman, A. B. Gelb, et al. In vivo Target Modulation and Biological Activity of CHIR-258, a Multitargeted Growth Factor Receptor Kinase Inhibitor, in Colon Cancer Models Clin. Cancer Res., May 15, 2005; 11(10): 3633 - 3641. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Tamborini, L. Bonadiman, T. Negri, A. Greco, S. Staurengo, P. Bidoli, U. Pastorino, M. A. Pierotti, and S. Pilotti Detection of Overexpressed and Phosphorylated Wild-Type Kit Receptor in Surgical Specimens of Small Cell Lung Cancer Clin. Cancer Res., December 15, 2004; 10(24): 8214 - 8219. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Th. Went, S. Dirnhofer, M. Bundi, M. Mirlacher, P. Schraml, S. Mangialaio, S. Dimitrijevic, J. Kononen, A. Lugli, R. Simon, et al. Prevalence of KIT Expression in Human Tumors J. Clin. Oncol., November 15, 2004; 22(22): 4514 - 4522. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Boldrini, S. Ursino, S. Gisfredi, P. Faviana, V. Donati, T. Camacci, M. Lucchi, A. Mussi, F. Basolo, R. Pingitore, et al. Expression and Mutational Status of c-kit in Small-Cell Lung Cancer: Prognostic Relevance Clin. Cancer Res., June 15, 2004; 10(12): 4101 - 4108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Raspollini, G. Amunni, A. Villanucci, P. Pinzani, L. Simi, M. Paglierani, and G. L. Taddei c-Kit Expression in Patients with Uterine Leiomyosarcomas: A Potential Alternative Therapeutic Treatment Clin. Cancer Res., May 15, 2004; 10(10): 3500 - 3503. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. C. Wolff, D. E. Randle, M. J. Egorin, J. D. Minna, and R. L. Ilaria Jr. Imatinib Mesylate Efficiently Achieves Therapeutic Intratumor Concentrations in Vivo but Has Limited Activity in a Xenograft Model of Small Cell Lung Cancer Clin. Cancer Res., May 15, 2004; 10(10): 3528 - 3534. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Raspollini, G. Amunni, A. Villanucci, G. Baroni, A. Taddei, and G. L. Taddei c-KIT expression and correlation with chemotherapy resistance in ovarian carcinoma: an immunocytochemical study Ann. Onc., April 1, 2004; 15(4): 594 - 597. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Casali, A. Stefani, G. Rossi, M. Migaldi, S. Bettelli, A. Parise, and U. Morandi The prognostic role of c-kit protein expression in resected large cell neuroendocrine carcinoma of the lung Ann. Thorac. Surg., January 1, 2004; 77(1): 247 - 252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Heinrich Is KIT an Important Therapeutic Target in Small Cell Lung Cancer?: Commentary re: B. E. Johnson et al., Phase II Study of Imatinib in Patients with Small Cell Lung Cancer. Clin. Cancer Res., 9: 5880-5887, 2003. Clin. Cancer Res., December 1, 2003; 9(16): 5825 - 5828. [Full Text] [PDF]
|
|
|
|
|
|
B. E. Johnson, T. Fischer, B. Fischer, D. Dunlop, D. Rischin, S. Silberman, M. O. Kowalski, D. Sayles, S. Dimitrijevic, C. Fletcher, et al. Phase II Study of Imatinib in Patients with Small Cell Lung Cancer Clin. Cancer Res., December 1, 2003; 9(16): 5880 - 5887. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. H. Blackhall, M. Pintilie, M. Michael, N. Leighl, R. Feld, M.-S. Tsao, and F. A. Shepherd Expression and Prognostic Significance of Kit, Protein Kinase B, and Mitogen-activated Protein Kinase in Patients with Small Cell Lung Cancer Clin. Cancer Res., June 1, 2003; 9(6): 2241 - 2247. [Abstract] [Full Text] [PDF]
|
|
| 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 |
