Clinical significance of MED12 expression in colorectal cancer

Yoshifumi Shimada, Yosuke Tajima, Hitoshi Kameyama, Ryoma Yagi, Takuma Okamura, Yuki Hirose, Jun Sakata, Takashi Kobayashi, Yasunobu Matsuda, Yoichi Ajioka, Shin Ichi Kosugi, Toshifumi Wakai

Research output: Contribution to journalArticlepeer-review


MED12 is a transcriptional mediator complex subunit, which negatively regulates the transforming growth factor β (TGF-β) pathway. The TGF-β pathway plays a major role in the induction of epithelial-mesenchymal transition (EMT). MED12 loss induces activation of the TGF-β pathway, resulting in EMT and drug resistance to epidermal growth factor receptor (EGFR)-targeted therapy. We aimed to investigate the clinical significance of MED12 loss detected by immunohistochemistry in patients with colorectal cancer (CRC). A total of 100 patients diagnosed with stage I-IV CRC were enrolled in this retrospective study. MED12 expression was evaluated immunohistochemically, and classified as either positive (≥20%) or negative (<20%) with regard to the percentage of immunoreactive cells. The relationships between MED12 loss and clinicopathological characteristics and RAS mutation status were analyzed. Overall, 79 and 21 patients were classified as MED12 positive and MED12 negative, respectively. MED12 negativity was significantly associated with tumor budding (P = 0.034), N category (P = 0.010), and M category (P = 0.031). Among stage IV CRC patients, 18 of 31 patients had the RAS wild-type gene; 6 of these patients were MED12 negative, and were considered to have the potential for resistance to EGFR-targeted therapy despite the presence of the wild-type gene. In conclusion, MED12 loss is associated with tumor budding, nodal metastasis, and distant metastasis in patients with CRC, suggesting that MED12 loss induces activation of the TGF-β pathway resulting in EMT. Future treatment strategies focusing on patients MED12 loss may improve the prognosis of patients with CRC.

Original languageEnglish
Pages (from-to)6937-6944
Number of pages8
JournalInternational Journal of Clinical and Experimental Pathology
Issue number7
Publication statusPublished - 2016

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Histology


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