David H Hwang1, Heather Sun2, Scott J Rodig1,2, Jason L Hornick1, Lynette M Sholl1. 1. Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. 2. Dana Farber/Harvard Cancer Center Pathology Core, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Abstract
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.
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.
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