P53 mutations in classic and pleomorphic invasive lobular carcinoma of the breast

Cigdem Ercan, Paul J. Van Diest, Bram Van Der Ende, John Hinrichs, Peter Bult, Horst Buerger, Elsken Van Der Wall, Patrick W.B. Derksen

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Background p53 is a tumor suppressor that is frequently mutated in human cancers. Although alterations in p53 are common in breast cancer, few studies have specifically investigated TP53 mutations in the breast cancer subtype invasive lobular carcinoma (ILC). Recently reported conditional mouse models have indicated that functional p53 inactivation may play a role in ILC development and progression. Since reports on the detection of TP53 mutations in the relatively favorable classic and more aggressive pleomorphic variants of ILC (PILC) are rare and ambiguous, we performed a comprehensive analysis to determine the mutation status of TP53 in these breast cancer subtypes. Methods To increase our understanding of p53-mediated pathways and the roles they may play in the etiology of classic ILC and PILC, we investigated TP53 mutations and p53 accumulation in a cohort of 22 cases of classic and 19 cases of PILC by direct DNA sequencing and immunohistochemistry. Results We observed 11 potentially pathogenic TP53 mutations, of which three were detected in classic ILC (13.6%) and 8 in PILC (42.1%; p=0.04). While p53 protein accumulation was not significantly different between classic and pleomorphic ILC, mutations that affected structure and protein function were significantly associated with p53 protein levels. Conclusion TP53 mutations occur more frequently in PILC than classic ILC.

Original languageEnglish (US)
Pages (from-to)111-118
Number of pages8
JournalCellular Oncology
Issue number2
StatePublished - Apr 2012
Externally publishedYes


  • Breast cancer
  • Classic
  • Invasive lobular breast cancer
  • Mutation
  • P53
  • Pleomorphic

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research


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