Frequent PIK3CA Mutations in Radial Scars
Katie Wolters, Daphne Ang, Andrea Warrick, Carol Beadling, Christopher Corless, Megan Troxell. Oregon Health & Science University, Portland, OR
Background: Radial scars are breast lesions of uncertain pathogenesis that are associated with a two-fold increased risk of breast cancer compared to controls. Activating point mutations in PIK3CA are found in 25-30% of invasive breast cancers; however, they have not previously been investigated in most non-carcinomatous lesions. We sought to evaluate radial scars for known activating point mutations commonly seen in invasive breast cancer.
Design: Sixteen surgical cases containing 24 distinct lesions were identified from pathology archives (2002-2010). Radial scars were intimately associated with a spectrum of epithelial morphology; 18 had non-atypical hyperplasia or columnar cell change, five had atypical ductal hyperplasia (ADH) or ductal carcinoma in situ (DCIS), and one had invasive ductal carcinoma (IDC). We also tested metastatic IDC in a lymph node in a patient with an unknown primary who had three discrete radial scars associated with non-atypical epithelium. Lesional tissue was macro-dissected from unstained paraffin sections; genomic DNA was then extracted and screened for a panel of known hotspot mutations using PCR and mass-spectroscopy analysis. The mutation panel covers 643 mutations in 53 genes, including AKT1/2/3, BRAF, CDK4, CTNNB1, EGFR, ERBB2, FBX4, FBXW7, FGFR1/2/3/4, GNAQ, HRAS, KIT, KRAS, MAP2K1/2/7, MET, NRAS, PDGFRA, PIK3CA, RET, SOS1, and TP53.
Results: Of the 24 lesions, 12 (50%) had PIK3CA mutations (11 with exon 20 H1047 mutations and one with an exon 9 E545K mutation). The remaining 12 lesions were wild-type for all of the screened genes. Of the radial scars without epithelial atypia, 9/18 (50%) had PIK3CA mutations; furthermore, 3/5 (60%) of radial scars with atypia had mutations detected. The IDC within a radial scar was wild-type. Interestingly, in the patient with three non-atypical radial scars and a positive lymph node, two of the radial scars as well as the metastatic IDC exhibited the PIK3CA exon 20 H1047R mutation whereas the third radial scar was wild-type. No other mutations were found with the extensive screening panel.
Conclusions: In this study, 50% of radial scars showed mutations in PIK3CA, which is notably higher than the 25-30% mutation frequency of invasive breast cancer. This finding raises interesting questions as to the role of PIK3CA mutations in breast cancer development. Additional larger studies are indicated to confirm and extend these observations in understanding the pathogenesis of radial scars and their relationship to breast cancer.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 44, Monday Morning