PTEN expression as a complementary biomarker for mismatch repair testing in breast cancer: International Journal of Molecular Sciences

G. Lopez, M. Noale, C. Corti, G. Gaudioso, E. Sajjadi, K. Venetis, D. Gambini, L. Runza, J. Costanza, C. Pesenti, F. Grossi, S. Maggi, S. Ferrero, S. Bosari, N. 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. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Original languageEnglish
JournalInt. J. Mol. Sci.
Issue number4
Publication statusPublished - 2020


  • Biomarkers
  • Breast cancer
  • Immunohistochemistry
  • Immunotherapy
  • Mismatch repair
  • PTEN
  • mismatch repair protein
  • phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase
  • tumor marker
  • PTEN protein, human
  • adult
  • algorithm
  • Article
  • cancer prognosis
  • cancer survival
  • controlled study
  • estrogen receptor positive breast cancer
  • female
  • gene amplification
  • gene dosage
  • human
  • human epidermal growth factor receptor 2 positive breast cancer
  • human tissue
  • immunohistochemistry
  • luminal A breast cancer
  • luminal B breast cancer
  • major clinical study
  • middle aged
  • mismatch repair
  • overall survival
  • predictive value
  • protein expression
  • real time polymerase chain reaction
  • tissue microarray
  • treatment outcome
  • wild type
  • aged
  • biosynthesis
  • breast tumor
  • clinical trial
  • disease free survival
  • gene expression regulation
  • metabolism
  • mortality
  • pathology
  • survival rate
  • very elderly
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor
  • Breast Neoplasms
  • Disease-Free Survival
  • DNA Mismatch Repair
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Middle Aged
  • PTEN Phosphohydrolase
  • Survival Rate


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