Mucinous breast carcinomas lack PIK3CA and AKT1 mutations

Elizabeth L. Kehr, Julie M. Jorns, Daphne Ang, Andrea Warrick, Tanaya Neff, Michelle Degnin, Rebecca Lewis, Carol Beadling, Christopher Corless, Megan Troxell

Research output: Contribution to journalArticle

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Abstract

Activating point mutations in the phosphatidylinositol-3-kinase catalytic subunit (PIK3CA) are among the most common molecular defects in invasive breast cancer. Point mutations in the downstream kinase AKT1 are seen in a minority of carcinomas. These mutations are found preferentially in estrogen receptor-positive and Her2-positive breast carcinomas; however, special morphologic types of breast cancer have not been well studied. Twenty-nine cases of pure invasive mucinous carcinoma and 9 cases of ductal carcinoma with mucinous differentiation were screened for a panel of point mutations (>321 mutations in 30 genes) using a multiplex polymerase chain reaction panel with mass spectroscopy readout. In addition, associated ductal carcinoma in situ, hyperplasia, or columnar cell lesions were separately tested where available (25 lesions). In 3 invasive cases and 15 ductal carcinoma in situ/proliferative lesions, PIK3CA hotspot mutations were, instead, tested by direct sequencing. No point mutations were identified in invasive mucinous breast carcinoma. This contrasts with the 35% frequency of PIK3CA mutations in a comparative group of invasive ductal carcinomas of no special type. Interestingly, PIK3CA hotspot point mutations were identified in associated ductal carcinoma in situ (3/14) and hyperplasia (atypical ductal hyperplasia [2/3], usual ductal hyperplasia [2/3], columnar cell change [1/5]), suggesting that PIK3CA mutations may play a role in breast epithelial proliferation. This series represents the largest study, to date, of PIK3CA genotyping in mucinous carcinoma and supports the unique pathogenetics of invasive mucinous breast carcinoma.

Original languageEnglish (US)
Pages (from-to)2207-2212
Number of pages6
JournalHuman Pathology
Volume43
Issue number12
DOIs
StatePublished - Dec 2012

Fingerprint

Mucinous Adenocarcinoma
Point Mutation
Carcinoma, Intraductal, Noninfiltrating
Breast Neoplasms
Mutation
Hyperplasia
Ductal Carcinoma
Phosphatidylinositol 3-Kinase
Multiplex Polymerase Chain Reaction
Mutation Rate
Estrogen Receptors
Mass Spectrometry
Catalytic Domain
Breast
Phosphotransferases
Carcinoma
Genes

Keywords

  • AKT1
  • Breast carcinoma
  • Ductal carcinoma in situ
  • Mucinous carcinoma
  • PIK3CA

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Kehr, E. L., Jorns, J. M., Ang, D., Warrick, A., Neff, T., Degnin, M., ... Troxell, M. (2012). Mucinous breast carcinomas lack PIK3CA and AKT1 mutations. Human Pathology, 43(12), 2207-2212. https://doi.org/10.1016/j.humpath.2012.03.012

Mucinous breast carcinomas lack PIK3CA and AKT1 mutations. / Kehr, Elizabeth L.; Jorns, Julie M.; Ang, Daphne; Warrick, Andrea; Neff, Tanaya; Degnin, Michelle; Lewis, Rebecca; Beadling, Carol; Corless, Christopher; Troxell, Megan.

In: Human Pathology, Vol. 43, No. 12, 12.2012, p. 2207-2212.

Research output: Contribution to journalArticle

Kehr, EL, Jorns, JM, Ang, D, Warrick, A, Neff, T, Degnin, M, Lewis, R, Beadling, C, Corless, C & Troxell, M 2012, 'Mucinous breast carcinomas lack PIK3CA and AKT1 mutations', Human Pathology, vol. 43, no. 12, pp. 2207-2212. https://doi.org/10.1016/j.humpath.2012.03.012
Kehr EL, Jorns JM, Ang D, Warrick A, Neff T, Degnin M et al. Mucinous breast carcinomas lack PIK3CA and AKT1 mutations. Human Pathology. 2012 Dec;43(12):2207-2212. https://doi.org/10.1016/j.humpath.2012.03.012
Kehr, Elizabeth L. ; Jorns, Julie M. ; Ang, Daphne ; Warrick, Andrea ; Neff, Tanaya ; Degnin, Michelle ; Lewis, Rebecca ; Beadling, Carol ; Corless, Christopher ; Troxell, Megan. / Mucinous breast carcinomas lack PIK3CA and AKT1 mutations. In: Human Pathology. 2012 ; Vol. 43, No. 12. pp. 2207-2212.
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