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

Megan L Troxell1, Alayne L Brunner, Tanaya Neff

  • 1Department of Pathology and Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA. troxellm@ohsu.edu

Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
|March 31, 2012
PubMed

Insights

Activating PIK3CA mutations are common in breast columnar cell lesions, occurring more frequently than in invasive breast cancer. These mutations are often discordant between columnar cell lesions and associated carcinomas, suggesting a complex role in breast carcinogenesis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The phosphatidylinositol-3-kinase (PI3K) pathway is frequently altered in invasive breast carcinoma, with mutations in PIK3CA (approximately 25%) and AKT1 (up to 5%).
  • Ductal carcinoma in situ and benign papillomas also exhibit similar mutations.
  • Activating point mutations in breast columnar cell lesions (CCLs) remain understudied.

Purpose of the Study:

  • To investigate the prevalence and patterns of activating point mutations in breast columnar cell lesions.
  • To compare the mutation status of CCLs with that of associated invasive carcinoma or carcinoma in situ.
  • To explore the potential role of PI3K/AKT pathway mutations in breast carcinogenesis and the precursor potential of CCLs.

Main Methods:

  • Analysis of 23 breast resection specimens containing columnar cell lesions, with 14 having associated invasive carcinoma or carcinoma in situ.
  • DNA extraction from formalin-fixed paraffin-embedded tissues.
  • Screening for 321 point mutations across 30 genes using multiplex PCR and mass spectrometry.

Main Results:

  • PIK3CA mutations were identified in 54% (13/24) of columnar cell lesions and 37% (3/8) of associated invasive carcinomas.
  • Mutation status between CCLs and their associated carcinomas was frequently discordant (only 5/14 cases shared the same genotype).
  • Five patients showed mutations in CCLs with wild-type carcinoma, and two had different mutations in CCLs versus carcinoma.

Conclusions:

  • The high prevalence of PIK3CA mutations in CCLs (50%) exceeds that reported in most invasive breast cancers.
  • Frequent discordance in PIK3CA/AKT1 mutation status between CCLs and carcinomas raises questions about their relationship.
  • These findings suggest PI3K/AKT pathway alterations may play a significant role in early breast carcinogenesis, highlighting the potential precursor role of CCLs.

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