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

摘要: Papillary lesions of the breast have an uncertain relationship to histogenesis carcinoma, and are thus diagnostically managerially challenging. Molecular genetic studies provided evidence that ductal carcinoma in situ even atypical hyperplasia precursors invasive carcinoma. However, papillary been seldom studied. We screened neoplasms for activating point mutations PIK3CA, AKT1, RAS protein-family members, which common carcinomas. DNA extracts were prepared from sections 89 lesions, including 61 benign papillomas (28 without significant hyperplasia; 33 with moderate florid hyperplasia), 11 hyperplasia, 7 situ, 10 Extracts PIK3CA AKT1 using mass spectrometry; cases negative further AKT2, BRAF, CDK, EGFR, ERBB2, KRAS, NRAS, HRAS. Mutations confirmed by sequencing or HPLC assay. A total 55 harbored (62%), predominantly (E17K, 27 cases) (exon 20 >exon 9, cases). Papillomas had more (54%) than (21%), whereas (42%) (15%) mutations, as did (PIK3CA 45%, 27%, NRAS 9%). Among seven three mutations. The carcinomas showed overall lower frequency 1 mutation (in a tumor arising papilloma), gene (Q61H), 2 (1 overlapping Q61H). These findings indicate approximately two-thirds driven PI3CA/AKT pathway. Some may arise these but others different molecular origins.