Correlation of CCND1 Amplification with Hormone Receptor (ER, PR) Expression and ERBB2 (Her2/neu) Gene Amplification in Invasive Ductal Carcinoma of the Breast: A Study of 102 Cases
MC Chang, IT Ocal, K Taneja, DA Dillon. Brigham & Women's Hospital; Harvard Medical School, Boston, MA; Mayo Clinic, Scottsdale, AZ
Background: The cyclin D1 gene (CCND1), located on human chromosome 11, is an important oncogene and is considered a major driver in breast carcinogenesis. Cyclin D1 is a downstream target of hormone receptors (ER, PR) and Her2/neu (ERBB2), important therapeutic markers in breast cancer classification. High levels of Cyclin D1 are associated with poor prognosis and therapeutic resistance in hormone-receptor positive cancers. However, the prevalence and significance of this abnormality in “Her2 positive” and “triple negative” breast cancers is poorly described. The purpose of this study is to evaluate CCND1 amplification in breast carcinoma by fluorescence in-situ hybridization (FISH), and to correlate these findings to ER, PR, and ERBB2 status in invasive ductal carcinomas of the breast.
Design: Consecutive cases of invasive ductal carcinoma of the breast were identified, tumor tissue was formalin-fixed and paraffin-embedded, tissue cores were obtained from multiple foci of each tumor, and tissue microarrays were prepared. Probes binding to either CCND1 (11q13) or ERBB2 (17q21-q22) and, respectively, chr 11or17 centromeric probes were used in FISH analysis of tissue microarray sections, with satisfactory signals achieved in 102 cases. Tumor cores were scored for CCND1 and ERBB2 amplification, defined as a signal ratio of 2.0 or greater. Results were correlated with ER and PR status determined by immunohistochemistry on whole tissue sections.
Results: Among 102 cases of invasive ductal carcinoma, 56 were ER+/Her2-, 15 were Her2+, and 31 were triple-negative. Overall, 12/102 demonstrated CCND1 amplification by FISH (12%). CCND1 amplification was seen in 12.5% (7/56) of ER positive/Her2 negative cases, 20% (3/15) of Her2 amplified cases and only 6% (2/31) of “triple negative” cases.
Conclusions: Findings demonstrate that CCND1 amplification is seen in invasive ductal carcinomas of all major subtypes, including ERBB2 amplified and triple negative breast cancers. Differences in the prevalence of CCND1 amplification among the subtypes did not achieve statistical significance in this study. Additional study of CCND1 amplification and its potential prognostic and therapeutic relevance in these less common subtypes is warranted.
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 17, Wednesday Afternoon