Increased insulin-like growth factor 1 receptor protein expression and gene copy number in small cell lung cancer
Andrzej Badzio1, Murry W Wynes, Rafal Dziadziuszko
1Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland.
Purpose:
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.
Insights
Small cell lung cancer frequently shows high insulin-like growth factor 1 receptor (IGF1R) protein expression and increased gene copy number. These findings suggest IGF1R as a potential therapeutic target for SCLC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Small cell lung cancer (SCLC) urgently requires novel therapeutic strategies.
- Insulin-like growth factor 1 receptor (IGF1R) is a tyrosine kinase receptor implicated in various cancers.
- Limited data exists on IGF1R expression, gene copy number, and prognostic significance in SCLC.
Purpose of the Study:
- To investigate IGF1R protein expression levels in SCLC.
- To determine IGF1R gene copy number and assess for gene amplification in SCLC.
- To evaluate the correlation between IGF1R features and clinicopathological factors in SCLC.
Main Methods:
- Analyzed IGF1R protein expression via immunohistochemistry (H-scores) in 84 primary SCLC tumors.
- Assessed IGF1R gene copy number using silver in situ hybridization in 81 primary SCLC tumors.
- Correlated IGF1R expression and gene copy number with patient age, tumor size, lymph node status, stage, and survival.
Main Results:
- Median IGF1R protein expression (H-score) was 88, with 74% of tumors showing positive immunostaining (H-score ≥ 10).
- Increased IGF1R gene copy number (≥4 copies/cell) was observed in 18.5% of cases, with gene amplification in 6.2%.
- A significant positive correlation was found between IGF1R protein expression and gene copy number (r=0.49, p<0.005); no association with clinicopathological factors or survival was detected.
Conclusions:
- SCLC frequently exhibits high IGF1R protein expression and increased gene copy number.
- Occasional true gene amplification of IGF1R was identified in SCLC.
- These molecular characteristics of IGF1R in SCLC hold potential significance for developing targeted anti-IGF1R therapies.
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