Using Caveolin-1 epithelial immunostaining patterns to stratify human breast cancer patients and predict the Caveolin-1 (P132L) mutation

Isabelle Mercier, Kelly G. Bryant, Federica Sotgia, Gloria Bonuccelli, Agnieszka K. Witkiewicz, Abhijit Dasgupta, Jean François Jasmin, Richard G. Pestell, Michael P. Lisanti

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Caveolin-1 (Cav-1) mutations, such as P132L, are associated with ER-positive human breast cancers. However, no immunohistochemical methods have yet been described to predict the presence of Cav-1 mutations in human breast cancer. Since the P132L mutation acts in a dominant-negative fashion and causes the mis-localization of Cav-1 in cultured cells in vitro, we hypothesized that of patients carrying this mutation would show a similar Cav-1 staining pattern in vivo. Indeed, while performing histological analysis of Cav-1 immunostaining on human breast cancer samples, we noted the emergence of two distinct epithelial staining patterns: (1) punctate peri-nuclear "Golgi-like" localization; or (2) diffuse cytoplasmic staining. The punctate peri-nuclear staining pattern was associated with ER-alpha positivity and was present mainly in well-differentiated samples. In striking contrast, the diffuse staining pattern was present in poorly differentiated samples, and was not associated with ER-status. DNA sequence analysis revealed that only well-differentiated samples with a punctate staining pattern harbored the Cav-1 P132L mutation. Thus, immunostaining of Cav-1 can be used as a first step to stratify human breast cancer patients and to predict the presence of Cav-1 mutations. As such, the punctate Cav-1 immunostaining pattern can now be used as a screening tool to select patients for Cav-1 mutational analysis.

Original languageEnglish (US)
Pages (from-to)1396-1401
Number of pages6
JournalCell Cycle
Volume8
Issue number9
DOIs
StatePublished - May 1 2009

Keywords

  • Breast cancer
  • Caveolin-1
  • Immunostaining patterns
  • P132L mutation

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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    Mercier, I., Bryant, K. G., Sotgia, F., Bonuccelli, G., Witkiewicz, A. K., Dasgupta, A., Jasmin, J. F., Pestell, R. G., & Lisanti, M. P. (2009). Using Caveolin-1 epithelial immunostaining patterns to stratify human breast cancer patients and predict the Caveolin-1 (P132L) mutation. Cell Cycle, 8(9), 1396-1401. https://doi.org/10.4161/cc.8.9.8307