PTEN Expression as a Complementary Biomarker for Mismatch Repair Testing in Breast Cancer.

Abstract

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.

• Authors: 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
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 4 (Feb 21 2020) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 32098071 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Biomarkers, Tumor
• PTEN Phosphohydrolase
• PTEN protein, human

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (biosynthesis)
• Breast Neoplasms (metabolism, mortality, pathology)
• DNA Mismatch Repair
• Disease-Free Survival
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Middle Aged
• PTEN Phosphohydrolase (biosynthesis)
• Survival Rate