The relationship between mismatch repair deficiency and PD-L1 expression in breast carcinoma

Anne M. Mills*, Erik A. Dill, Christopher A. Moskaluk, Jaroslaw Dziegielewski, Tim N. Bullock, Patrick M. Dillon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


Mismatch repair (MMR) deficiency in solid tumors has recently been linked to susceptibility to immunotherapies targeting the programmed cell death-1 (PD-1)/programmed cell death-1 ligand (PD-L1) axis. Loss of MMR proteins has been shown to correlate with tumoral PD-L1 expression in colorectal and endometrial carcinomas, but the association between expression of MMR proteins and PD-L1 has not previously been studied in breast carcinoma, where MMR deficiency is less common. We assessed the relationship between PD-L1 and MMR protein expression by immunohistochemistry in 245 primary and 40 metastatic breast carcinomas. Tumoral staining for PD-L1 was positive in 12% of all cases, including 32% of triple-negative cancers. MMR deficiency was observed in 0.04% of breast cancers; the single MMR-deficient case was a high-grade, triplenegative ductal carcinoma which showed dual loss of MLH1 and PMS2 proteins and expressed PD-L1. Two ER+ carcinomas initially were scored with MMR protein loss in tissue microarray format but were subsequently shown to beMMR-intact on whole sections. Analysis of MMR gene mutation in The Cancer Genome Atlas corroborates low frequency of MMR deficiency for invasive breast cancer. MMR protein expression is therefore unlikely to show utility as a screen for immunotherapeutic vulnerability in this tumor type, and may provoke unwarranted genetic testing in patients unlikely to have a heritable cancer syndrome. PD-L1 may be a more clinically relevant biomarker for anti-PD-1/PD-L1 therapies in this setting.

Original languageEnglish
Pages (from-to)183-191
Number of pages9
JournalAmerican Journal of Surgical Pathology
Issue number2
StatePublished - 2018
Externally publishedYes


  • Breast cancer
  • Breast carcinoma
  • Immunotherapy
  • Mismatch repair
  • Mismatch repair deficiency
  • PD-L1


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