American Journal of Pathology
American Journal of Pathology
5 years ago

Mutational analysis of AKT1 and PIK3CA in intraductal papillomas of the breast with special reference to cellular components

The pathological feature of intraductal papillomas is defined as a papillary structure composed of a fibrovascular stromal core lined by luminal epithelial cells and myoepithelial cells. We used droplet digital PCR for the mutational analysis of AKT1 (E17K) and PIK3CA (H1047R, E542K, and E545K) in 60 papillomas. AKT1 and PIK3CA mutations were detected in 12 (20%) and 17 (28%) of the papillomas, respectively. In five tumors harboring mutations, mutational analysis of AKT1 or PIK3CA was performed separately using luminal epithelial cells and myoepithelial cells sorted using anti-CK19 antibody and anti-SMA antibody. The two types of cells from a given papilloma were found to have the identical mutation. Three patients with the PIK3CA mutation–positive papilloma developed breast cancers at the resection site of the papilloma but none of these subsequent breast cancers had the PIK3CA mutation. These results indicate that a papilloma stems from a bipotent progenitor cell which contains the AKT1 or PIK3CA mutation and proliferates and differentiates to form the papilloma. Papilloma can be a risk factor for developing breast cancer but is unlikely to be its obligate precursor.

Publisher URL: www.sciencedirect.com/science

DOI: S0002944017305436

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