論文

査読有り 国際誌
2020年5月24日

Microsatellite instability and mismatch repair protein expressions in lymphocyte-predominant breast cancer.

Cancer science
  • Yoshiya Horimoto
  • ,
  • May Thinzar Hlaing
  • ,
  • Harumi Saeki
  • ,
  • Shigehisa Kitano
  • ,
  • Katsuya Nakai
  • ,
  • Ritsuko Sasaki
  • ,
  • Aiko Kurisaki-Arakawa
  • ,
  • Atsushi Arakawa
  • ,
  • Naomi Otsuji
  • ,
  • Shuji Matsuoka
  • ,
  • Emi Tokuda
  • ,
  • Masami Arai
  • ,
  • Mitsue Saito

記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1111/cas.14500

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.

リンク情報
DOI
https://doi.org/10.1111/cas.14500
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32449246

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