Myc protein expression correlates with MYC amplification in small-cell lung carcinoma
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Published on: December 31, 2014
David H Hwang1, Heather Sun2, Scott J Rodig1,2
1Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Aims:
Myc family members are important contributors to oncogenesis in a variety of tumours. Identification of therapeutic targets is needed in small-cell lung carcinoma (SCLC), an aggressive disease with limited treatment options. Sequencing studies have identified MYC amplification in 2-7% of SCLCs. This study aims to determine the rate of MYC gene amplification and its correlation with Myc protein overexpression in SCLC.
Methods And Results:
One hundred and three cases of formalin-fixed, paraffin-embedded SCLC were examined. Myc protein expression was scored according to the extent of immunohistochemical staining. MYC copy number (CN) was evaluated with dual-colour chromogenic in-situ hybridization (CISH) for the MYC locus and a chromosome 8 (Chr8) centromeric control. Amplification was defined as a MYC/Chr8 ratio of ≥2. Thirty-eight per cent of SCLCs had some degree of Myc protein expression, and 9% of cases were MYC-amplified. MYC CN was significantly correlated with the extent of Myc protein expression (Spearman's ρ = 0.57, P < 0.01). There was no significant association between Myc expression or CN and clinicopathological features.
Conclusions:
MYC amplification by CISH was identified in 9% of SCLCs, and correlated with protein expression. As novel Myc-targeted therapies are developed, CISH and IHC should be considered as biomarkers of Myc pathway dysregulation in SCLC.
Insights
In 9% of small-cell lung carcinoma (SCLC) cases, MYC gene amplification was detected and correlated with Myc protein overexpression. These findings support MYC amplification as a potential biomarker for novel SCLC therapies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Myc family proteins are key oncogenic drivers in various cancers.
- Small-cell lung carcinoma (SCLC) is an aggressive malignancy with limited therapeutic strategies.
- MYC amplification occurs in 2-7% of SCLC cases, necessitating further investigation.
Purpose of the Study:
- To ascertain the frequency of MYC gene amplification in SCLC.
- To evaluate the correlation between MYC gene amplification and Myc protein overexpression.
- To identify potential therapeutic targets in SCLC.
Main Methods:
- Examined 103 formalin-fixed, paraffin-embedded SCLC samples.
- Assessed Myc protein expression using immunohistochemistry (IHC).
- Determined MYC copy number (CN) via chromogenic in-situ hybridization (CISH) relative to chromosome 8.
Main Results:
- Myc protein expression was observed in 38% of SCLCs.
- MYC amplification (MYC/Chr8 ratio ≥2) was identified in 9% of cases.
- A significant correlation was found between MYC CN and Myc protein expression (Spearman's ρ = 0.57, P < 0.01).
Conclusions:
- MYC amplification occurs in 9% of SCLCs and is linked to protein overexpression.
- CISH and IHC can serve as biomarkers for Myc pathway dysregulation in SCLC.
- Further development of Myc-targeted therapies for SCLC is warranted.
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