Clin Endosc.  2019 Sep;52(5):464-471. 10.5946/ce.2018.181.

Immunohistochemical Expression of Epithelial-Mesenchymal Transition Markers in Early Gastric Cancer: Cancer Tissue versus Noncancer Tissue

Affiliations
  • 1Digestive Disease Center and Research Institute, Soonchunhyang University College of Medicine, Bucheon, Korea. sjhong@schmc.ac.kr

Abstract

BACKGROUND/AIMS
Epithelial-mesenchymal transition (EMT) is a developmental process, wherein the epithelial cells show reduced intercellular adhesions and acquire migratory fibroblastic properties. EMT is associated with downregulation in epithelial marker expression, abnormal translocation of E-cadherin, and upregulation in mesenchymal marker expression. Here, we investigated the immunohistochemical (IHC) expression of EMT markers in early gastric cancer (EGC) between cancer and noncancer tissues.
METHODS
Tissue samples were prospectively obtained from 19 patients with EGC that underwent endoscopic submucosal dissection (ESD). We compared the expression level of transforming growth factor (TGF)-β, vascular endothelial growth factor (VEGF), E-cadherin, α-smooth muscle actin (α-SMA), and vimentin between cancer and noncancer tissues using IHC. Among the 19 patients, 15 patients had follow-up biopsy at 3 months after ESD for EGC.
RESULTS
Cancer tissues presented higher values of EMT mesenchymal markers (α-SMA/vimentin/TGF-β/VEGF) than the noncancerous tissues (p<0.05) that were significantly low after ESD (p<0.05). No significant correlation was reported for tumor location and initial Helicobacter pylori infection.
CONCLUSIONS
The mesenchymal expression of EMT markers was higher in the cancerous tissues than in the noncancer tissues.

Keyword

Epithelial-mesenchymal transition; Immunohistochemistry; Early gastric cancer; Endoscopic submucosal dissection

MeSH Terms

Actins
Biopsy
Cadherins
Down-Regulation
Epithelial Cells
Epithelial-Mesenchymal Transition*
Fibroblasts
Follow-Up Studies
Helicobacter pylori
Humans
Immunohistochemistry
Prospective Studies
Stomach Neoplasms*
Transforming Growth Factors
Up-Regulation
Vascular Endothelial Growth Factor A
Vimentin
Actins
Cadherins
Transforming Growth Factors
Vascular Endothelial Growth Factor A
Vimentin

Figure

  • Fig. 1. Flow chart of study design. α-SMA, α-smooth muscle actin; EGC, early gastric cancer; ESD, endoscopic submucosal dissection; F/U, follow-up; IHC, immunohistochemical; TGF-β, transforming growth factor-β; VEGF, vascular endothelial growth factor.

  • Fig. 2. Immunohistochemical staining of noncancer tissue and cancer tissue. Representative expression of proteins studied by immunohistochemistry (original magnification ×200). This figure shows noncancer tissue and cancer tissues. (A, B) transforming growth factor-β, (C, D) VEGF, (E, F) E-cadherin, (G, H) α-smooth muscle actin, and (I, J) vimentin.


Cited by  1 articles

Aberrant Expression of Epithelial-Mesenchymal Transition Markers in Early Gastric Cancer: Clinical Application
Moon Kyung Joo
Clin Endosc. 2019;52(5):393-394.    doi: 10.5946/ce.2019.139.


Reference

1. Lee HJ, Lee YJ, Lee JY, et al. Characteristics of synchronous and metachronous multiple gastric tumors after endoscopic submucosal dissection of early gastric neoplasm. Clin Endosc. 2018; 51:266–273.
Article
2. Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell. 2009; 139:871–890.
Article
3. Natalwala A, Spychal R, Tselepis C. Epithelial-mesenchymal transition mediated tumourigenesis in the gastrointestinal tract. World J Gastroenterol. 2008; 14:3792–3797.
Article
4. López-Novoa JM, Nieto MA. Inflammation and EMT: an alliance towards organ fibrosis and cancer progression. EMBO Mol Med. 2009; 1:303–314.
Article
5. Zhu Y, Wu J, Ma W, Zhang H, Wang D. Expression of TGF-β1, Snail, E-cadherin and N-cadherin in gastric cancer and its significance. Chinese Journal of Clinical Oncology. 2007; 4:384–389.
Article
6. Murai T, Yamada S, Fuchs BC, et al. Epithelial-to-mesenchymal transition predicts prognosis in clinical gastric cancer. J Surg Oncol. 2014; 109:684–689.
Article
7. Thiery JP, Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol. 2006; 7:131–142.
Article
8. Shook D, Keller R. Mechanisms, mechanics and function of epithelial-mesenchymal transitions in early development. Mech Dev. 2003; 120:1351–1383.
Article
9. Radisky DC. Epithelial-mesenchymal transition. J Cell Sci. 2005; 118:4325–4326.
Article
10. Yang J, Mani SA, Weinberg RA. Exploring a new twist on tumor metastasis. Cancer Res. 2006; 66:4549–4552.
11. Ryu HS, Park DJ, Kim HH, Kim WH, Lee HS. Combination of epithelial-mesenchymal transition and cancer stem cell-like phenotypes has independent prognostic value in gastric cancer. Hum Pathol. 2012; 43:520–528.
Article
12. Xu GF, Zhang WJ, Sun Q, Xu X, Zou X, Guan W. Combined epithelial-mesenchymal transition with cancer stem cell-like marker as predictors of recurrence after radical resection for gastric cancer. World J Surg Oncol. 2014; 12:368.
Article
13. Xiao Q, Li L, Xie Y, et al. Transcription factor E2F-1 is upregulated in human gastric cancer tissues and its overexpression suppresses gastric tumor cell proliferation. Cell Oncol. 2007; 29:335–349.
Article
14. Lazăr D, Tăban S, Ardeleanu C, et al. The immunohistochemical expression of E-cadherin in gastric cancer; correlations with clinicopathological factors and patients’ survival. Rom J Morphol Embryol. 2008; 49:459–467.
15. Han JP, Hong SJ, Kim HK, et al. Expression of immunohistochemical markers according to histological type in patients with early gastric cancer. Scand J Gastroenterol. 2016; 51:60–66.
Article
16. Cong H, Yao RY, Sun ZQ, et al. DNA hypermethylation of the vimentin gene inversely correlates with vimentin expression in intestinal- and diffuse-type gastric cancer. Oncol Lett. 2016; 11:842–848.
Article
17. Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer. 2002; 2:442–454.
Article
18. Nakayama H, Enzan H, Miyazaki E, Toi M. Alpha smooth muscle actin positive stromal cells in gastric carcinoma. J Clin Pathol. 2002; 55:741–744.
Article
19. Grigore D, Simionescu CE, Stepan A, et al. Assessment of CD105, alpha-SMA and VEGF expression in gastric carcinomas. Rom J Morphol Embryol. 2013; 54(3 Suppl):701–707.
20. Huang L, Wu RL, Xu AM. Epithelial-mesenchymal transition in gastric cancer. Am J Transl Res. 2015; 7:2141–2158.
21. Choi YJ, Kim N, Chang H, et al. Helicobacter pylori-induced epithelial-mesenchymal transition, a potential role of gastric cancer initiation and an emergence of stem cells. Carcinogenesis. 2015; 36:553–563.
Article
22. Zang M, Zhang B, Zhang Y, et al. CEACAM6 promotes gastric cancer invasion and metastasis by inducing epithelial-mesenchymal transition via PI3K/AKT signaling pathway. PLoS One. 2014; 9:e112908.
Article
23. Zaravinos A. The regulatory role of microRNAs in EMT and cancer. J Oncol. 2015; 2015:865816.
Article
24. Garber K. Epithelial-to-mesenchymal transition is important to metastasis, but questions remain. J Natl Cancer Inst. 2008; 100:232–233. , 239.
Article
Full Text Links
  • CE
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr