Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

EphB1 and Ephrin-B, New Potential Biomarkers for Squamous Cell/adenosquamous Carcinomas and Adenocarcinomas of the Gallbladder

  • Yuan, Yuan (Department of Pathology, Third Xiangya Hospital, Central South University) ;
  • Yang, Zhu-Lin (Research Laboratory of Hepatobiliary Diseases, Second Xiangya Hospital, Central South University) ;
  • Miao, Xiong-Ying (Research Laboratory of Hepatobiliary Diseases, Second Xiangya Hospital, Central South University) ;
  • Liu, Zi-Ru (Research Laboratory of Hepatobiliary Diseases, Second Xiangya Hospital, Central South University) ;
  • Li, Dai-Qiang (Department of Pathology, Second Xiangya Hospital, Central South University) ;
  • Zou, Qiong (Department of Pathology, Third Xiangya Hospital, Central South University) ;
  • Li, Jing-He (Department of Pathology, Basic School of Medicine, Central South University) ;
  • Liang, Lu-Feng (Department of Hepatobiliary and Pancreatic Surgery, Hunan Provincial People's Hospital) ;
  • Zeng, Gui-Xiang (Department of Pathology, Loudi Central Hospital) ;
  • Chen, Sen-Lin (Department of Pathology, Hunan Provincial Tumor Hospital)
  • Published : 2014.02.01
Download PDF
⟨ Previous Next ⟩

Abstract

Squamous cell/adenosquamous carcinoma (SC/ASC) of the gallbladder are rare tumors and there are few clinical reports in the literature. Herein we report our clinical experience with 46 patients with SC/ASC and 80 with adenocarcinoma (AC). Expression of EphB1 and Ephrin-B in each tumor was determined using immunohistochemical methods for determination of correlations with prognosis. There was no difference in EphB1 and Ephrin-B expression between SC/ASC and AC tumors (P>0.05), but greater expression in those less than 3 cm in diameter, stage I or II (TNM stage), with no lymph node metastases, with no local invasion and treated with radical resection was apparent. Expression of EphB1 (P<0.05) and Ephrin-B (P<0.01) was higher in well differentiated than in poorly differentiated AC tumors. Kaplan-Meier survival analysis indicated that degree of differentiation, tumor diameter, lymph node metastases, local invasion, surgical approach and expression rate of EphB1 and Ephrin-B were closely related to the survival of SC/ASC (P<0.05) and AC patients (P<0.01). Patients with tumors that positive expressed EphB1 and Ephrin-B, whether it is SC/ASC ($P_{SC/ASC}$ =0.000) or AC ($P_{AC}$ =0.000 or $P_{AC}$ =0.002) had longer survival than those negative expression. Cox multivariate analysis indicated a negative correlation between expression of EphB1 or Ephrin-B and overall survival. Hence, EphB1 and Ephrin-B could be regarded as independent good prognostic factorsand important biological markers for SC/ASC and AC of gallbladder.

Keywords

References

  1. Batlle E , Bacant J, Begthel H, et al (2005). EphB receptor activity suppresses colorectal cancer progression. Nature, 435, 1126-30. https://doi.org/10.1038/nature03626
  2. Chan KM, Yu MC, Lee WC, Jan YY, Chen MF (2007). Adenosquamous/squamous cell carcinoma of gallbladder. J Surg Oncol, 95, 129-34. https://doi.org/10.1002/jso.20576
  3. Chen J, Zhuang G, Frieden L, Debinski W (2008). Eph receptors and Ephrins in cancer: common themes and controversies. Cancer Res, 68, 10031-3. https://doi.org/10.1158/0008-5472.CAN-08-3010
  4. Davalos V, Dopeso H, Castano J, et al (2006). EphB4 and survival of colorectal cancer patients. Cancer Res, 66, 8943-8. https://doi.org/10.1158/0008-5472.CAN-05-4640
  5. Eph Nomenclature Committee (1997). Unified nomenclature for Eph family receptors and their ligands, the ephrins. Cell, 90, 403. https://doi.org/10.1016/S0092-8674(00)80500-0
  6. Fu T, Li P, Wang H, et al (2009). c-Rel is a transcriptional repressor of EPHB2 in colorectal cancer. J Pathol, 219, 103-13. https://doi.org/10.1002/path.2590
  7. Genander M, Halford MM, Xu NJ, et al (2009). Dissociation of EphB2 signaling pathways mediating progenitor cell proliferation and tumor suppression. Cell, 139, 679-92. https://doi.org/10.1016/j.cell.2009.08.048
  8. Guo DL, Zhang J, Yuen ST, et al (2006). Reduced expression of EphB2 that parallels invasion and metastasis in colorectal tumours. Carcinogenesis, 27, 454-64. https://doi.org/10.1093/carcin/bgi259
  9. Hamdani NH, Qadri SK, Aggarwalla R, et al (2012). Clinicopathological study of gallbladder carcinoma with special reference to gallstones:our 8-year experience from eastern India. Asian Pac J Cancer Prev, 13, 5613-7. https://doi.org/10.7314/APJCP.2012.13.11.5613
  10. Huang J, Xiao D, Li G, et al (2013). EphA2 promotes epithelialmesenchymal transition through the Wnt/${\beta}$-catenin pathway in gastric cancer cells. Oncogene, 10, 238.
  11. Jubb AM, Zhong F, Bheddah S, et al (2005). EphB2 is a prognostic factor in colorectal cancer. Clin Cancer Res, 11, 5181-7. https://doi.org/10.1158/1078-0432.CCR-05-0143
  12. Kalita D, Pant L, Singh S, et al (2013). Impact of routine histopathological examination of gall bladder specimens on early detection of malignancy - a study of 4,115 cholecystectomy specimens. Asian Pac J Cancer Prev, 14, 3315-8. https://doi.org/10.7314/APJCP.2013.14.5.3315
  13. Kapoor VK (2006). Gallbladder cancer: a global perspective. J Surg Oncol, 93, 607-9. https://doi.org/10.1002/jso.20525
  14. Kayaharan M, Nagakawa T (2007). Recent trends of gallbladder cancer in Japan: an analysis of 4, 770 patients. Cancer, 110, 572-80. https://doi.org/10.1002/cncr.22815
  15. Kim WS, Jang KT, Choi DW, et al (2011). Clinicopathologic analysis of adenosquamous /squamous cell carcinoma of the gallbladder. J Surg Oncol, 103, 239-42. https://doi.org/10.1002/jso.21813
  16. Kumar JR, Tewari M, Rai A, el al (2006). An objective assessment of demography of gallbladder cancer. Surg Oncol, 93, 610-4. https://doi.org/10.1002/jso.20526
  17. Lugli A, Spichtin H, Maurer R, et al (2005). EphB2 expression across 138 human tumor types in a tissue microarray: high levels of expression in gastrointestinal cancers. Clin Cancer Res, 11, 6450-8. https://doi.org/10.1158/1078-0432.CCR-04-2458
  18. Mao YY, Jing FY, Jin MJ, et al (2013). rs12904 polymorphism in the 3'UTR of EFNA1 is associated with colorectal cancer susceptibility in a Chinese population. Asian Pac J Cancer Prev, 14, 5037-41. https://doi.org/10.7314/APJCP.2013.14.9.5037
  19. Miao H, Li DQ, Mukherjee A, et al (2009). EphA2 mediates ligand-dependent inhibition and ligand-independent promotion of cell migration and invasion via a reciprocal regulatory loop with Akt. Cancer Cell, 16, 9-20. https://doi.org/10.1016/j.ccr.2009.04.009
  20. Murai KK, Pasquale EB (2003). 'Eph'ective signaling: forward, reverse and crosstalk. J Cell Sci, 116, 2823-32. https://doi.org/10.1242/jcs.00625
  21. Nakada M, Niska JA, Tran NL, McDonough WS, Berens ME (2005). EphB2/R-Ras signaling regulates glioma cell adhesion, growth, and invasion. Am J Pathol, 167, 565-76. https://doi.org/10.1016/S0002-9440(10)62998-7
  22. Nakada M, Niska JA, Miyamori H, et al (2004). The phosphorylation of EphB2 receptor regulates migration and invasion of human glioma cells. Cancer Res, 64, 3179-85. https://doi.org/10.1158/0008-5472.CAN-03-3667
  23. Palmer A, Klein R (2003). Multiple roles of ephrins in morphogenesis, neuronal networking, and brain function. Genes Dev, 17, 1429-50. https://doi.org/10.1101/gad.1093703
  24. Senior PV, Zhang BX, Chan ST (2010). Loss of cell-surface receptor EphB2 is important for the growth, migration, and invasiveness of a colon cancer cell line. Int J Colorectal Dis, 25, 687-94. https://doi.org/10.1007/s00384-010-0916-7
  25. Wu Q, Suo Z, Risberg B, et al (2004). Expression of Ephb2 and Ephb4 in breast carcinoma. Pathol Oncol Res, 10, 26-33. https://doi.org/10.1007/BF02893405

Cited by

  1. Galectin-9: An anticancer molecule for gallbladder carcinoma vol.48, pp.3, 2016, https://doi.org/10.3892/ijo.2016.3347