PTEN expression as a complementary biomarker for mismatch repair testing in breast cancer

Gianluca Lopez, Marianna Noale, Chiara Corti, Gabriella Gaudioso, Elham Sajjadi, Konstantinos Venetis, Donatella Gambini, Letterio Runza, Jole Costanza, Chiara Pesenti, Francesco Grossi, Stefania Maggi, Stefano Ferrero, Silvano Bosari, Nicola Fusco

Research output: Contribution to journalArticlepeer-review


Mismatch repair (MMR) analysis in breast cancer may help to inform immunotherapy decisions but it lacks breast-specific guidelines. Unlike in other neoplasms, MMR protein loss shows intra-tumor heterogeneity and it is not mirrored by microsatellite instability in the breast. Additional biomarkers can improve MMR clinical testing. Phosphatase and tensin homolog (PTEN) inactivation is an early oncogenic event that is associated with MMR deficiency (dMMR) in several tumors. Here, we sought to characterize the diagnostic utility of PTEN expression analysis for MMR status assessment in breast cancer. A total of 608 breast cancers were profiled for their MMR and PTEN status. Proteins expression and distribution were analyzed by immunohistochemistry (IHC) on tissue microarrays and confirmed on full sections; PTEN copy number alterations were detected using a real-time PCR assay. Overall, 78 (12.8%) cases were MMR-heterogeneous (hMMR), while all patterns of PTEN expression showed no intra-tumor heterogeneity. Wild-type PTEN expression was observed in 15 (18.5%) dMMR tumors (p < 0.0001). Survival analyses revealed significant correlations between MMR-proficient (pMMR), PTEN expression, and a better outcome. The positive predictive value of PTEN-retained status for pMMR ranged from 94.6% in estrogen receptor (ER)+/HER2-tumors to 100% in HER2-amplified and ER-/HER2-cases. We propose a novel diagnostic algorithm where PTEN expression analysis can be employed to identify pMMR breast cancers.

Original languageEnglish
Article number1461
JournalInternational Journal of Molecular Sciences
Issue number4
Publication statusPublished - Feb 2 2020


  • Biomarkers
  • Breast cancer
  • Immunohistochemistry
  • Immunotherapy
  • Mismatch repair
  • PTEN

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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