Cortactin Gene Amplification and Expression in Breast Cancer
MA Lopez-Garcia, FC Geyer, MB Lambros, R Vatcheva, R Natrajan, KK Dedes, JS Reis-Filho. ICR, London, United Kingdom
Background: 11q13 amplification is found in up to 15% of breast cancers. Multiple genes, including cyclin D1, map to the smallest region of amplification of 11q13. Out of these genes, cortactin (CTTN) has been shown to be consistently overexpressed at the mRNA level in tumours harbouring 11q13 amplification. The aims of this study were twofold: to determine whether CTTN is overexpressed at the protein level in tumours harbouring 11q13 amplification and to define the correlations between cortactin overexpression and gene amplification with clinicopathological features of breast cancers and survival of breast cancer patients.
Design: A cohort of 245 patients with invasive breast cancer treated with therapeutic surgery followed by adjuvant anthracycline-based chemotherapy were included in a tissue microarray containing two replicate cores. Immunohistochemistry was performed with a monoclonal antibody against CTTN and semi-quantitatively assessed using the 'quick score' system (intensity 0-3 x distribution 0-6), with observers blinded to 11q13 status and clinicopathological features. CTTN expression levels were classified as low <5, intermediate 5-10, high ≥12. Chromogenic in situ hybridisation (CISH) with probes mapping to the 11q13 smallest region of amplification was performed with observers blinded to CTTN expression levels and clinicopathological features. Amplification was defined as >5 signals per nucleus or large gene copy clusters in more than 50% of cancer cells.
Results: Amplification of 11q13 was observed in 12% of cases. High CTTN expression was found in 11% of cases. A strong correlation between 11q13 amplification and CTTN expression levels was found (Mann-Whitney U test, p<0.00001). Out of the 27 cases harbouring 11q13 amplification, only 1 had CTTN expression levels < 5. After p value adjustment for multiple comparisons, neither CTTN expression levels nor 11q13 amplification showed significant associations with clinicopathological features. Although both cyclin D1 and CTTN were significantly expressed at higher levels in cases harbouring 11q13 amplification, no correlation between cyclin D1 and CTTN expression levels was found. CTTN expression and 11q13 amplification were not associated with survival.
Conclusions: CTTN is expressed at higher levels in breast cancers harbouring 11q13 amplification, suggesting that CTTN may also be one of the drivers of this amplicon. However CTTN expression is not associated with the outcome of breast cancer patients treated with anthracycline-based chemotherapy.
Monday, March 22, 2010 1:00 PM
Poster Session II # 59, Monday Afternoon