Phosphatidylinositol-3-kinase pathway mutations are common in breast columnar cell lesions

Megan Troxell, Alayne L. Brunner, Tanaya Neff, Andrea Warrick, Carol Beadling, Kelli Montgomery, Shirley Zhu, Christopher Corless, Robert B. West

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29 Scopus citations

Abstract

The phosphatidylinositol-3-kinase pathway is one of the most commonly mutated pathways in invasive breast carcinoma, with PIK3CA mutations in 25% of invasive carcinomas, and AKT1 mutations in up to 5%. Ductal carcinoma in situ, and benign papillomas harbor similar mutations. However, activating point mutations in breast columnar cell lesions have been infrequently studied. Twenty-three breast resection specimens containing columnar cell lesions were identified; 14 with associated invasive carcinoma or carcinoma in situ. DNA extracts were prepared from formalin-fixed paraffin-embedded tissue and screened for a panel of point mutations (321 mutations in 30 genes) using a multiplex PCR panel with mass-spectroscopy readout. PIK3CA mutations were identified in 13/24 columnar cell lesions (54%) and 3/8 invasive carcinomas (37%). The mutation status of columnar cell lesions and associated carcinoma was frequently discordant. Of the 14 cases, only 5 demonstrated the same genotype in matched samples of columnar cell lesions and carcinoma (4 wild type, 1 PIK3CA H1047R). Interestingly, five patients had mutations in columnar cell lesions with wild-type carcinoma; two patients had different point mutations in columnar cell lesions and carcinoma. Only three cases had wild-type columnar cell lesion and mutated carcinoma. The 50% PIK3CA mutation prevalence in columnar cell lesions is greater than reported in most studies of invasive breast cancer. Further, columnar cell lesions and carcinoma were frequently discordant for PIK3CA/AKT1 mutation status. These findings raise interesting questions about the role of PIK3CA/AKT pathway in breast carcinogenesis, and the biologic/precursor potential of columnar cell lesions.

Original languageEnglish (US)
Pages (from-to)930-937
Number of pages8
JournalModern Pathology
Volume25
Issue number7
DOIs
Publication statusPublished - Jul 2012

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Keywords

  • breast cancer
  • columnar cell lesion
  • PIK3CA

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Troxell, M., Brunner, A. L., Neff, T., Warrick, A., Beadling, C., Montgomery, K., ... West, R. B. (2012). Phosphatidylinositol-3-kinase pathway mutations are common in breast columnar cell lesions. Modern Pathology, 25(7), 930-937. https://doi.org/10.1038/modpathol.2012.55