Somatic mutations and increased lymphangiogenesis observed in a rare case of intramucosal gastric carcinoma with lymph node metastasis

Naoki Ikari, Shota Aoyama, Akiyoshi Seshimo, Yuji Suehiro, Tomoko Motohashi, Shohei Mitani, Sawako Yoshina, Etsuko Tanji, Akiko Serizawa, Takuji Yamada, Kiyoaki Taniguchi, Masakazu Yamamoto, Toru Furukawa

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Abstract

Background and aim: Intramucosal gastric adenocarcinoma of the wellmoderately differentiated type only exhibits lymph node metastasis in extremely rare cases. We encountered such case and investigated both the lymphangiogenic properties and somatic mutations in the cancer to understand the prometastatic features of early-stage gastric cancer. Methods: We quantitatively measured the density of lymphatic vessels and identified mutations in 412 cancer-associated genes through next-generation target resequencing of DNA extracted from tumor cells in a formalin-fixed and paraffinembedded tissue. Functional consequence of the identified mutation was examined in vitro by means of gene transfection, immunoblot, and the quantitative real-time polymerase chain reaction assay. Results: The intramucosal carcinoma was accompanied by abundant lymphatic vessels. The metastatic tumor harbored somatic mutations in NBN, p.P6S, and PAX8, p.R49H. The PAX8R49H showed significantly higher transactivation activity toward E2F1 than the wild-type PAX8 (P < 0.001). Conclusions: Our data suggest that increased lymphangiogenesis and somatic mutations of NBN and/or PAX8 could facilitate lymph node metastasis from an intramucosal gastric carcinoma. These findings may potentially inform evaluations of the risk of developing lymph node metastasis in patients with intramucosal gastric cancer.

Original languageEnglish
Pages (from-to)10808-10817
Number of pages10
JournalOncotarget
Volume9
Issue number12
DOIs
Publication statusPublished - 2018

Keywords

  • Early gastric cancer
  • Lymph node metastasis
  • Lymphangiogenesis
  • NBN
  • PAX8

ASJC Scopus subject areas

  • Oncology

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    Ikari, N., Aoyama, S., Seshimo, A., Suehiro, Y., Motohashi, T., Mitani, S., Yoshina, S., Tanji, E., Serizawa, A., Yamada, T., Taniguchi, K., Yamamoto, M., & Furukawa, T. (2018). Somatic mutations and increased lymphangiogenesis observed in a rare case of intramucosal gastric carcinoma with lymph node metastasis. Oncotarget, 9(12), 10808-10817. https://doi.org/10.18632/oncotarget.24289