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The pathologic 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-cytokeratin 19 antibody and anti-α smooth muscle actin antibody. The two types of cells from a given papilloma had 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 that 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., (Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Two types of quantitative assay kits for K-ras mutations, PCR-preferential homoduplex formation assay (PHFA) and enriched PCR and enzyme-linked mini-sequence assay (ELMA), were recently developed. The K-ras mutations were analyzed using these assays., Materials and Methods: DNA was extracted from the pancreatic juice which was obtained by endoscopy from 38 patients with pancreatic neoplasms (23 adenocarcinomas and 15 intraductal papillary neoplasms) and from 62 without it., Results: The results of the two methods were mutually correlative. K-ras mutation was detected at high levels (mutant ras genes occupied >2% of all K-ras genes) in 25 of the 38 cases (66%) with pancreatic neoplasm. It was also detected at high levels in 9 of the 14 cases (64%) with pancreatic cyst. In contrast, the mutant gene was detected at a lower level (<2%) in other cases., Conclusions: Quantitative analysis of the mutant ras gene provided a useful tool for diagnosing the pancreatic carcinoma when the percentage of the mutant is high, especially when the types of mutation were either GAT or GTT., (Copyright 2002 Elsevier Science B.V.)

Clonality of solitary intraductal papillomas of the breast was analyzed using a method based on restriction fragment length polymorphism of the X-chromosome-linked phosphoglycerokinase (PGK) gene and on random inactivation of the gene by methylation. The application of polymerase chain reaction to this method enabled clonal analysis of such a small intraductal lesion as papilloma. Clonal analysis of DNA samples obtained from the nine solitary intraductal papillomas and adjacent normal breast tissues showed that all of the papillomas were monoclonal and all the normal breast tissues were polyclonal in origin. When DNA samples were obtained from four widely separated sites in the papillomas, clonal analysis showed that all were monoclonal and, in addition, the same allele of PGK gene was inactivated in each case. These results demonstrate that solitary intraductal papilloma arises as a single monoclonal tumor and extends along the ducts rather than occurring as multicentric monoclonal tumors and merging together subsequently. Immunohistochemical staining of smooth muscle alpha-actin, a marker protein of myoepithelial cells, revealed that solitary intraductal papilloma was composed of approximately equal mixtures of luminal epithelial and myoepithelial cells. Since solitary intraductal papillomas were shown to be monoclonal in origin, it was suggested that this disease originates from a common precursor that could differentiate into both luminal epithelial and myoepithelial cells.