ORIGINAL ARTICLE

MYC amplification in breast cancer: a chromogenic in situ hybridisation study

S Maria Rodriguez-Pinilla¹, Robin L Jones¹, Maryou B K Lambros¹, Edurne Arriola¹, Kay Savage¹, Michelle James¹, Sarah E Pinder² and Jorge S Reis-Filho¹

¹ The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK
² Department of Histopathology, Addenbrooke’s Hospital, Cambridge, UK

Correspondence to:
Correspondence to:
Dr Jorge S Reis-Filho
The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, Fulham Road, London SW3 6JB, UK; Jorge.Reis-Filho{at}icr.ac.uk

Aims: To analyse the correlation between MYC amplification and various clinicopathological features and outcome in a cohort of 245 patients with invasive breast carcinoma treated with surgery followed by anthracycline-based chemotherapy. Given the high prevalence of MYC amplification in tumours of BRCA1 mutation carriers and the similarities between these and sporadic "basal-like" carcinomas, the prevalence of MYC amplification in "basal-like" breast carcinomas was investigated.

Methods: MYC gene copy number was assessed on tissue microarrays containing duplicate cores of 245 invasive breast carcinomas by means of chromogenic in situ hybridisation using SpotLight C-MYC amplification probe and chromosome 8 centromeric probe (CEP8). Signals were evaluated at 400x magnification; 30 morphologically unequivocal neoplastic cells in each core were counted for the presence of the gene and CEP8 probes.

Results: Amplification was defined as a MYC:CEP8 ratio >2. Signals for both MYC and CEP8 were assessable in 196/245 (80%) tumours. MYC amplification was found in 19/196 cases (9.7%) and was not associated with tumour size, histological grade, positivity for oestrogen receptor, progesterone receptor, HER2, epidermal growth factor, cytokeratins 14, 5/6 and 17, MIB1 or p53. Only 4% of basal-like carcinomas showed MYC amplification, compared to 8.75% and 10.7% of luminal and HER2 tumours respectively. On univariate analysis, MYC amplification displayed a significant association with shorter metastasis-free and overall survival and proved to be an independent prognostic factor on multivariate survival analysis.

Conclusion: MYC amplification is not associated with "basal-like" phenotype and proved to be an independent prognostic factor for breast cancer patients treated with anthracycline-based chemotherapy.

Abbreviations: CEP8, chromosome 8 centromeric probe; CISH, chromogenic in situ hybridisation; Ck, cytokeratin; EGFR, epidermal growth factor receptor; ER, oestrogen receptor; FISH, fluorescent in situ hybridisation; PR, progesterone receptor

Keywords: oncogene; MYC; CISH; prognosis; basal-like breast cancer

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