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Strong Expression and Amplification of IGF1R in Pleuropulmonary Blastomas
Christian Vokuhl1, Laura de Leon-Escapini1, Ivo Leuschner1
11 Department of Pediatric Pathology, Christian-Albrechts-University Kiel, Kiel, Germany.
Insights
Pleuropulmonary blastoma (PPB) genetics reveal chromosome 8 gains in 44% and IGF1R gene amplification in 25% of cases. IGF1R amplification is linked to advanced type 3 PPB, suggesting it as a therapeutic target.
Area of Science:
- Pediatric Oncology
- Cancer Genetics
- Tumorigenesis
Background:
- Pleuropulmonary blastoma (PPB) is a rare pediatric intrathoracic malignancy.
- PPB subtypes include cystic (Type 1), mixed (Type 2), and solid (Type 3) lesions.
- The genetic underpinnings of PPB remain largely unexplored.
Purpose of the Study:
- To investigate the genetic alterations in pediatric Pleuropulmonary blastoma.
- To evaluate the expression of insulin-like growth factor type 1 receptor (IGF1R) in PPB.
- To correlate genetic findings with PPB subtypes and potential therapeutic targets.
Main Methods:
- Comparative genomic hybridization (CGH) on 16 PPB cases.
- Fluorescence in situ hybridization (FISH) to confirm genetic changes.
- Immunohistochemistry for IGF1R protein expression analysis.
Main Results:
- Frequent CGH findings included losses on 4q, 5q, 9p and gains on chromosomes 8, 17, 20q.
- Confirmed 44% (7/16) gain of chromosome 8 and 25% (4/16) amplification of the IGF1R gene.
- IGF1R amplification occurred exclusively in Type 3 PPBs, while chromosome 8 gains were observed in Type 2 and Type 3 tumors.
- All but one PPB case exhibited IGF1R protein expression.
Conclusions:
- Chromosome 8 gains appear to be early events in PPB development, occurring in both Type 2 and Type 3 tumors.
- IGF1R gene amplification, observed in Type 3 PPBs, suggests a later event in tumor progression.
- Strong IGF1R protein expression indicates its potential as a therapeutic target for chemoresistant PPBs.
Abstract:
Pleuropulmonary blastoma (PPB) is a rare malignant intrathoracic tumor primarily affecting children under 5 years of age. PPBs are histologically divided into 3 subtypes: Type 1 PPBs are composed of multiple cysts, and type 3 is a solid lesion with a variable morphologic appearance. Type 2 has a mixed morphology consisting of cystic and solid areas. The genetics of PPB are poorly understood. We analyzed 16 cases of the Kiel Paediatric Tumor Registry with the diagnosis of PPB by comparative genomic hybridization and confirmed some genetic changes by fluorescence in situ hybridization. Furthermore, we performed immunohistochemistry to evaluate insulin-like growth factor type 1 (IGF1R) protein expression. Frequent findings by comparative genomic hybridization were losses on 4q, 5q, 9p and gains on chromosome 8, 17, and 20q. Genomic amplification was observed in 5 cases, 4 related to 15q25qter and 1 to 1p. Fluorescence in situ hybridization could confirm 7 gains of chromosome 8 (7/16, 44%) and 4 amplifications of the IGF1R-gene on 15q26 (4/16, 25%). All of the tumors with IGF1R amplification were type 3 PPBs. One of the PPBs with gain of chromosome 8 was a type 2 tumor and 6 tumors were type 3 PPBs. All but one PPB showed an IGF1R expression by immunohistochemistry. In our series of 16 PPBs, 25% of the tumors have an amplification of the IGF1R gene and 44% show a gain of chromosome 8. All of the tumors with IGF1R amplification were PPBs type 3, indicating that it is a later event in tumor progression, while the gain of chromosome 8 was found in both type 2 and type 3 tumors indicating that these changes are probably earlier events in tumor development. Furthermore, the strong IGF1R protein expression could be a possible therapeutic target in refractory chemoresistant PPBs.