Coexpression of fragile histidine triad and c-kit is relevant for prediction of survival in patients with small cell lung cancer.
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.
Rehfeld
Nina
N
Klinik für Hämatologie, Onkologie und klinische Immunologie, Heinrich-Heine-Universität Düsseldorf, Dusseldorf, Germany.
Geddert
Helene
H
Atamna
Abedelsalam
A
Gabbert
Helmut E
HE
Steidl
Ulrich
U
Fenk
Roland
R
Kronenwett
Ralf
R
Haas
Rainer
R
Rohr
Ulrich-Peter
UP
D017766:Acid Anhydride Hydrolases / Q000096:biosynthesis / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000401:mortality*; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D016016:Proportional Hazards Models; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis / Q000235:genetics*; D012189:Retrospective Studies; D016896:Treatment Outcome; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D007770:L-Lactate Dehydrogenase; D009363:Neoplasm Proteins; D019009:Proto-Oncogene Proteins c-kit; D000099170:Bis(5'-adenosyl)triphosphatase