Our results provide oncologists with a highly accurate laboratory method to identify biological predictors of the efficacy of different therapies, and they may have an important impact on clinical practice. This method may be particularly useful in patients with advanced/metastatic NSCLC.

Purpose: The c-kit protein, also known as CD117, is a member of the type III receptor tyrosine kinase family. Kinase activity has been implicated in the pathophysiology of many tumors, including small-cell lung carcinoma (SCLC). Autocrine or paracrine activation of c-kit by its ligand has been postulated for lung cancer, but this receptor can also be activated by mutations of the c-kit gene. We examined c-kit expression and mutational status in SCLC to verify its putative expression and genetic alterations, as well as its eventual prognostic impact.Experimental Design: We studied 60 SCLC samples to determine the mutations of the coding region of the gene; the exons 9 and 11 were analyzed by PCR-single-strand conformational polymorphism and automated sequencing. Moreover, c-kit expression was evaluated in 55 samples by immunohistochemical method.Results: Expression of c-kit was demonstrated in about 40% of SCLC samples. Two mutations in exon 9 and three mutations in exon 11 were found. Kaplan-Meier analysis revealed no prognostic significance of c-kit expression for survival.Conclusions: In our series, the expression of c-kit and its mutational status failed to appear relevant or to have a significant impact on survival; this makes the therapeutic approach with an inhibitor of tyrosine kinase more difficult in SCLC until a sure demonstration of c-kit implication is obtained for this tumor.

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Human telomerase is a structurally complex ribonucleoprotein that is responsible for the maintenance of telomeric DNA at the ends of the chromosomes. The enzyme is proposed as having an important role in cell immortalization and oncogenesis. A limited number of studies have been performed on the telomerase system in brain tumors, and these studies are somewhat conflicting. The relative ineffectiveness of current therapies for malignant gliomas led to the need for novel targets for more promising approaches. In order to clarify the prognostic significance of telomerase expression in gliomas and to speculate on therapeutic implications, we examined telomerase activity by the telomeric repeat amplification protocol (TRAP) assay in 42 gliomas, (32 multiform glioblastomas, 4 anaplastic astrocytomas, 4 differentiated astrocytomas, 1 oligoastrocytoma and 1 oligosarcoma). Telomerase messenger expression (hTERT mRNA) was evaluated by reverse transcription-PCR analysis in the same group of tumors. High telomerase activity was detected in 21/42 gliomas (50%). The levels of telomerase in terms of its messenger level expression overlapped the activity; in fact, a significant association between telomerase activity and hTERT mRNA expression was found (¯2 test; p<0.0001). At univariate analysis, advanced age as well as high telomerase activity and hTERT mRNA levels were seen to be significant predictors of worse prognosis regarding both overall survival (p=0.007, p=0.007, p=0.04, respectively) and disease-free interval (p=0.008, p=0.008, p=0.04, respectively). All these variables maintained a significant independent prognostic role in multivariate analysis. Telomerase may represent an indicator of progression and poor prognosis in this type of cancer, with interesting therapeutic implications.

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