Phosphorylated mTOR expression correlates with podoplanin expression and high tumor grade in esophageal squamous cell carcinoma

Wen Yu Chuang, Yu Sun Chang, Yin Kai Chao, Chi Ju Yeh, Shir Hwa Ueng, Chiu Yueh Chang, Yun Hen Liu, Chen Kan Tseng, Hsien Kun Chang, Yung Liang Wan, Chuen Hsueh*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

9 Scopus citations


Mechanistic (or mammalian) target of rapamycin (mTOR) plays important roles in cell growth and proliferation. In esophageal squamous cell carcinoma (SCC), high expression of phosphorylated (activated) mTOR (p-mTOR) has been reported as an adverse prognostic factor in some but not all studies. The signals of mTOR pathway and mitogen-activated protein kinase (MAPK) pathway converge on 4E-binding protein 1 (4EBP1), which drives the downstream proliferative signals. We previously found that high expression of phosphorylated 4EBP1 (p-4EBP1) is an adverse prognostic factor in esophageal SCC. Podoplanin is a type-1 transmembrane glycoprotein expressed in various normal human tissues, including lymphatic endothelium. Our previous study showed that high podoplanin expression correlates with clinical nodal metastasis, which is associated with short survival in esophageal SCC. In current study, we investigated p-mTOR expression by immunohistochemistry in 75 cases of surgically resected esophageal SCC. The result was correlated with p-4EBP1 expression, podoplanin expression, clinicopathologic features and patient survival. We found that high p-mTOR expression was significantly associated with high podoplanin expression (P = 0.0030) and high tumor grade (P = 0.0014). No correlation with p-4EBP1 expression, patient survival or other clinicopathologic features was found. Recently, podoplanin expression in astrocytic brain tumors was found to be regulated by the phosphatidylinositol 3-kinase (PI3K)/AKT/activator protein-1 (AP-1) pathway. Similarly, mTOR is activated by a PI3K/AKT/mTOR pathway. The association of p-mTOR and podoplanin expression in our study could be due to a common upstream pathway. Since both mTOR and podoplanin are potential therapeutic targets, the possible benefit of combined targeted therapy warrants further investigation.

Original languageEnglish
Pages (from-to)12757-12765
Number of pages9
JournalInternational Journal of Clinical and Experimental Pathology
Issue number10
StatePublished - 2015


  • 4E-binding protein 1 (4EBP1)
  • Esophagus
  • Mechanistic target of rapamycin (mTOR)
  • Podoplanin
  • Squamous cell carcinoma
  • Tumor grade


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