High prevalence of PIK3CA/AKT pathway mutations in papillary neoplasms of the breast

Papillary lesions of the breast have an uncertain relationship to the histogenesis of breast carcinoma, and are thus diagnostically and managerially challenging. Molecular genetic studies have provided evidence that ductal carcinoma in situ and even atypical ductal hyperplasia are precursors of invasive carcinoma. However, papillary lesions have been seldom studied. We screened papillary breast neoplasms for activating point mutations in PIK3CA, AKT1, and RAS protein-family members, which are common in invasive ductal carcinomas. DNA extracts were prepared from sections of 89 papillary lesions, including 61 benign papillomas (28 without significant hyperplasia; 33 with moderate to florid hyperplasia), 11 papillomas with atypical ductal hyperplasia, 7 papillomas with carcinoma in situ, and 10 papillary carcinomas. Extracts were screened for PIK3CA and AKT1 mutations using mass spectrometry; cases that were negative were further screened fo