Invasive Mucinous Breast Carcinomas Lack PIK3CA/AKT Pathway Mutations.
Elizabeth Kehr, Andrea Warrick, Tanaya Neff, Rebecca Lewis, Michelle Degnin, Carol Beadling, Christopher Corless, Megan Troxell. OHSU, Portland, OR
Background: Activating mutations in the PIK3CA/AKT signal transduction pathway are found in 25-30% of invasive breast cancers, making PIK3CA one of the most commonly mutated gene in breast cancer. Lobular carcinomas have an even higher mutation frequency, but other special types of breast cancer have not been systematically investigated. Invasive mucinous breast carcinoma is characterized by tumor cells secreting and floating in pools of mucin, and when pure, tend to have a favorable prognosis. We sought to evaluate invasive mucinous carcinomas for known activating point mutations.
Design: Fifteen cases of invasive mammary mucinous carcinoma/carcinoma with mucinous features were identified from pathology archives (2002-2010). Lesional tissue was macrodissected from unstained paraffin sections; areas of more solid invasive carcinoma, or precursor lesions were separately isolated in 4 of the cases. Genomic DNA was extracted and screened for a panel of known hotspot mutations using PCR and mass-spectroscopy analysis (Sequenom MassARRAY). The mutation panel covers 321 mutations in 30 genes, including ABL, AKT1/2/3, BRAF, CDK4, CTNNB1, EGFR1, ERBB2, FBX4, FBXW7, FGFR1/2/3, FLT3, GNAQ, HRAS, JAK2, KIT, KRAS, MAPK2K1/2, MET, NRAS, PDGFRA, PIK3CA, PTPN11, RET, SOS1, and TP53.
Results: Of the 15 invasive carcinomas, none had activating point mutations in PIK3CA, AKT, or genes encoding other targeted signaling proteins. The S8R substitution in the FBX4 gene, a ubiquitin ligase, was identified in one invasive mucinous carcinoma; however, this is thought to be a single nucleotide polymorphism, with unknown significance. Interestingly, an activating PIK3CA exon 20 mutation (H1047R) was identified in a focus of columnar cell lesion/flat epithelial atypia, but was not found in the same patient's invasive mucinous carcinoma.
Conclusions: The lack of PIK3CA/AKT mutations in this series of mammary mucinous carcinomas (0%) is markedly lower than the 25-30% mutation frequency reported in invasive ductal carcinomas, implying that the pathogenetics of mammary mucinous carcinomas may be unique. Further larger studies are indicated to confirm and extend these observations.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 25, Tuesday Afternoon