Expression and mutational status of c-kit in small-cell lung cancer: prognostic relevance.
OBJECTIVE
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.


METHODS
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.
Boldrini
Laura
L
Departments of Surgery, Oncology, Transplants and Advanced Technologies in Medicine, and Cardio-Thoracic Surgery, University of Pisa, Pisa, Italy.
Ursino
Silvia
S
Gisfredi
Silvia
S
Faviana
Pinuccia
P
Donati
Valentina
V
Camacci
Tiziano
T
Lucchi
Marco
M
Mussi
Alfredo
A
Basolo
Fulvio
F
Pingitore
Raffaele
R
Fontanini
Gabriella
G
D000328:Adult; D000368:Aged; D018288:Carcinoma, Small Cell / Q000175:diagnosis / Q000235:genetics*; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012737:Sex Factors; D015398:Signal Transduction; D013997:Time Factors
D004247:DNA; D019009:Proto-Oncogene Proteins c-kit