Clinical features and impact of p53 status on sporadic mismatch repair deficiency and Lynch syndrome in uterine cancer

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  • Mayumi Kobayashi Kato
    Division of Genome Biology National Cancer Center Research Institute Tokyo Japan
  • Erisa Fujii
    Division of Genome Biology National Cancer Center Research Institute Tokyo Japan
  • Yuka Asami
    Division of Genome Biology National Cancer Center Research Institute Tokyo Japan
  • Yukihide Momozawa
    Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences Yokohama Japan
  • Kengo Hiranuma
    Division of Genome Biology National Cancer Center Research Institute Tokyo Japan
  • Masaaki Komatsu
    Division of Medical AI Research and Development National Cancer Center Research Institute Tokyo Japan
  • Ryuji Hamamoto
    Division of Medical AI Research and Development National Cancer Center Research Institute Tokyo Japan
  • Takahiro Ebata
    Department of Epigenomics, Life Science Tokyo Advanced Research Center Hoshi University Tokyo Japan
  • Koji Matsumoto
    Department of Obstetrics and Gynecology Showa University School of Medicine Tokyo Japan
  • Mitsuya Ishikawa
    Department of Gynecology National Cancer Center Hospital Tokyo Japan
  • Takashi Kohno
    Division of Genome Biology National Cancer Center Research Institute Tokyo Japan
  • Tomoyasu Kato
    Department of Gynecology National Cancer Center Hospital Tokyo Japan
  • Hiroshi Yoshida
    Department of Diagnostic Pathology National Cancer Center Hospital Tokyo Japan
  • Kouya Shiraishi
    Division of Genome Biology National Cancer Center Research Institute Tokyo Japan

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<jats:title>Abstract</jats:title><jats:p>The clinical features of sporadic mismatch repair deficiency (MMRd) and Lynch syndrome (LS) in Japanese patients with endometrial cancer (EC) were examined by evaluating the prevalence and prognostic factors of LS and sporadic MMRd in patients with EC. Targeted sequencing of five LS susceptibility genes (<jats:italic>MLH1</jats:italic>, <jats:italic>MSH2</jats:italic>, <jats:italic>MSH6</jats:italic>, <jats:italic>PMS2</jats:italic>, and <jats:italic>EPCAM</jats:italic>) was carried out in 443 patients with EC who were pathologically diagnosed with EC at the National Cancer Center Hospital between 2011 and 2018. Pathogenic variants in these genes were detected in 16 patients (3.7%). Immunohistochemistry for MMR proteins was undertaken in 337 of the 433 (77.9%) EC patients, and 91 patients (27.0%) showed absent expression of at least one MMR protein. The 13 cases of LS with MMR protein loss (93.8%) showed a favorable prognosis with a 5‐year overall survival (OS) rate of 100%, although there was no statistically significant difference between this group and the sporadic MMRd group (<jats:italic>p</jats:italic> = 0.27). In the MMRd without LS group, the 5‐year OS rate was significantly worse in seven patients with an aberrant p53 expression pattern than in those with p53 WT (53.6% vs. 93.9%, log‐rank test; <jats:italic>p</jats:italic> = 0.0016). These results suggest that p53 abnormalities and pathogenic germline variants in MMR genes could be potential biomarkers for the molecular classification of EC with MMRd.</jats:p>

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