Increased insulin-like growth factor 1 receptor protein expression and gene copy number in small cell lung cancer.
OBJECTIVE
Identification of new therapies in small cell lung cancer (SCLC) is urgently needed. Insulin-like growth factor 1 receptor (IGF1R) is a tyrosine kinase receptor implicated in the pathogenesis of several malignancies and is potentially an attractive target for anticancer treatment. Knowledge about IGF1R protein expression, gene copy number, and the prognostic relevance of these features in SCLC is limited.


METHODS
We analyzed IGF1R protein expression and gene copy number in primary tumors from 90 patients with SCLC (67 men and 23 women) who underwent pulmonary resection. IGF1R expression assessed by immunohistochemistry with H scores from 0 to 400 was evaluable in 84 patients and IGF1R gene copy number assessed by silver in situ hybridization technique in 81 patients.


RESULTS
Median H score for IGF1R protein expression was 88 (range, 0-400), and the proportion of positive immunostaining using cutoff H score of 10 was 74%. Increased IGF1R gene copy number (an average of four or more copies per cell) was found in 15 cases (18.5%), five of whom (6.2%) showed gene amplification. There was a significant correlation between protein expression and gene copy number (r = 0.49, p < 0.005). IGF1R expression and gene copy number did not associate with clinicopathological factors such as patient age, tumor size, lymph node involvement, stage, and survival.


CONCLUSIONS
SCLC is characterized by frequent high-IGF1R protein expression, increased gene copy number, and occasional occurrence of true gene amplification. These features may have important implications for future anti-IGF1R therapeutic approaches.
Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland.
Andrzej
A
Badzio
Murry W
MW
Wynes
Rafal
R
Dziadziuszko
Daniel T
DT
Merrick
Marta
M
Pardo
Witold
W
Rzyman
Anna
A
Kowalczyk
Shalini
S
Singh
James
J
Ranger-Moore
Guadalupe
G
Manriquez
Fabien
F
Gaire
Jacek
J
Jassem
Fred R
FR
Hirsch
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D018628:Gene Dosage; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D017526:Receptor, IGF Type 1 / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology; D015398:Signal Transduction; D055752:Small Cell Lung Carcinoma / Q000737:chemistry / Q000235:genetics* / Q000628:therapy
D017526:Receptor, IGF Type 1