Open AccessMicrosatellite instability and mismatch repair protein expressions in lymphocyte‐predominant breast cancer
Author(s) -
Horimoto Yoshiya,
Thinzar Hlaing May,
Saeki Harumi,
Kitano Shigehisa,
Nakai Katsuya,
Sasaki Ritsuko,
KurisakiArakawa Aiko,
Arakawa Atsushi,
Otsuji Naomi,
Matsuoka Shuji,
Tokuda Emi,
Arai Masami,
Saito Mitsue
Publication year - 2020
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14500
Subject(s) - microsatellite instability , dna mismatch repair , breast cancer , lymphocyte , instability , genome instability , lymphocyte activation , cancer research , cancer , medicine , biology , oncology , immunology , microsatellite , immune system , genetics , dna , physics , dna damage , gene , colorectal cancer , t cell , mechanics , allele
The frequency of microsatellite instability (MSI) is reportedly extremely low in breast cancer, despite widespread clinical expectations that many patients would be responsive to immune‐checkpoint inhibitors (ICI). Considering that some triple‐negative breast cancers (TNBC) responded well to ICI in a clinical trial and that a high density of tumor‐infiltrating lymphocytes (TILs) is frequently observed in other cancers with high levels of microsatellite instability (MSI‐H), we hypothesized that some TNBC with a high density of TILs would be MSI‐H. Medullary carcinoma (MedCa) of the breast, a rare histological type, is characterized by a high density of TILs. Considering that MedCa of the colon is often MSI‐H, we suspected that MedCa in breast cancer might also include MSI‐H tumors. Therefore, we conducted MSI tests on such breast cancers with a high density of TILs. The MSI status of 63 TIL‐high TNBC and 38 MedCa tumors, all from Asian women who had undergone curative surgery, were determined retrospectively. DNA mismatch repair (MMR) proteins and PD‐L1 expression were also investigated immunohistochemically. All samples were microsatellite stable, being negative for all microsatellite markers. TIL‐high TNBC with low MLH1 protein had higher levels of PD‐L1 in stromal immune cells ( P = .041). MedCa tumors showed significantly higher PD‐L1 expression in immune cells than in TIL‐high TNBC (<.001). We found that MSI‐H tumors were absent in TIL‐high breast cancers. Examination of MMR proteins, not a purpose of Lynch syndrome screening, may merit further studies to yield predictive information for identifying patients who are likely to benefit from ICI.