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


CONCLUSIONS
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.
Rodriguez-Pinilla
S Maria
SM
The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK.
Jones
Robin L
RL
Lambros
Maryou B K
MB
Arriola
Edurne
E
Savage
Kay
K
James
Michelle
M
Pinder
Sarah E
SE
Reis-Filho
Jorge S
JS
D018943:Anthracyclines / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000235:genetics* / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D002863:Chromogenic Compounds; D005260:Female; D005784:Gene Amplification / Q000235:genetics; D016259:Genes, myc; D006801:Humans; D008408:Mastectomy; D011379:Prognosis; D016019:Survival Analysis; D046888:Tissue Array Analysis / Q000379:methods; D016896:Treatment Outcome
D018943:Anthracyclines; D000970:Antineoplastic Agents; D002863:Chromogenic Compounds