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Coexpression of Fragile Histidine Triad and c-kit Is Relevant for Prediction of Survival in Patients with Small Cell Lung Cancer

¹ Klinik für Hämatologie, Onkologie und klinische Immunologie and ² Institut für Pathologie, Heinrich-Heine-Universität Düsseldorf, Dusseldorf, Germany and ³ Harvard Institutes of Medicine and Harvard Stem Cell Institute, Boston, Massachusetts

Requests for reprints: Ulrich-Peter Rohr, Klinik für Hämatologie, Onkologie und klinische Immunologie, Heinrich-Heine-Universität Düsseldorf, Moorenstraße 5, D-40225 Dusseldorf, Germany. Phone: 49211-8117720; Fax: 49211-8118853. E-mail: urohr-uni-duesseldorf{at}gmx.de

Background: In a retrospective analysis of 195 patients with small cell lung cancer (SCLC), we examined the prognostic value of a coexpression of fragile histidine triad (FHIT) protein and c-kit on patient's survival.

Methods: As assessed by immunohistochemistry using formalin-fixed, paraffin-embedded tissue sections, tumors of 195 patients with SCLC were evaluated for FHIT and c-kit coexpression.

Results: Coexpression of FHIT and c-kit was observed in 53.3%; a positive expression of either FHIT or c-kit was found in 40.5%. Complete lack of FHIT and c-kit (6.2%) was associated with a significantly shorter survival time for the patients with a mean of 122 ± 45 days compared with 468 ± 89 days for patients with lung cancer coexpressing FHIT and c-kit (P = 0.0011). The proportion of FHIT- and c-kit-positive cells within a tumor was also related to survival time. Patients with tumors with a proportion between 0% to 25% of FHIT- and c-kit-positive cells had the worst survival of 157 ± 34 days compared with 496 ± 95 days for patients showing >25% FHIT- and c-kit-positive cells (P = 0.0002). Further, variables associated with shorter survival times were low performance status, elevated lactate dehydrogenase level, and advanced tumor stage according to tumor-node-metastasis classification. Multivariate analysis using Cox regression model, including 11 variables, confirmed the prognostic significance of a combined expression of FHIT and c-kit next to tumor stage, performance status, and lactate dehydrogenase level.

Conclusions: Differential FHIT and c-kit expression was of prognostic relevance for survival in patients with SCLC and therefore provide useful variables for therapeutic decisions. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2232–8)