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Postoperative Prognostic Predictors of Bile Duct Cancers: Clinical Analysis and Immunoassays of Tissue Microarrays

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Background/Aims: Cholangiocarcinoma frequently recurs even after curative resection. Expression levels of proteins such as epidermal growth factor receptor (EGFR), Snail, epithelial cadherin (E-cadherin), and interleukin-6 (IL-6) examined by immunohistochemistry have been studied as potential prognostic factors for cholangiocarcinoma. The aim of this study was to investigate significant factors affecting the prognosis of resectable cholangiocarcinoma. Methods: Ninety-one patients who underwent surgical resection at Samsung Medical Center for cholangiocarcinoma from 1995 to 2013 were included in this study. Expression levels of E-cadherin, Snail, IL-6, membranous EGFR, and cytoplasmic EGFR were analyzed by immunohistochemistry using tissue microarray blocks made from surgical specimens. Results: Patients with high levels of membranous EGFR in tissue microarrays had significantly shorter overall survival (OS) and disease-free survival (DFS): high membranous EGFR (score 0–2) 38.0 months versus low membranous EGFR (score 3) 14.4 months (p=0.008) and high membranous EGFR (score 0–2) 23.2 months versus low membranous EGFR (score 3) 6.1 months (p=0.004), respectively. On the other hand, E-cadherin, Snail, cytoplasmic EGFR, and IL-6 did not show significant association with OS or DFS. Patients with distant metastasis had significantly higher IL-6 levels than those with locoregional recurrence (p=0.01). Conclusions: This study showed that overexpression of membranous EGFR was significantly associated with shorter OS and DFS in surgically resected bile duct cancer patients. In addition, higher IL-6 expression was a predictive marker for recurrence in cholangiocarcinoma patients with distant organ metastasis after surgical resection.

Abstract

Background/Aims: Cholangiocarcinoma frequently recurs even after curative resection. Expression levels of proteins such as epidermal growth factor receptor (EGFR), Snail, epithelial cadherin (E-cadherin), and interleukin-6 (IL-6) examined by immunohistochemistry have been studied as potential prognostic factors for cholangiocarcinoma. The aim of this study was to investigate significant factors affecting the prognosis of resectable cholangiocarcinoma. Methods: Ninety-one patients who underwent surgical resection at Samsung Medical Center for cholangiocarcinoma from 1995 to 2013 were included in this study. Expression levels of E-cadherin, Snail, IL-6, membranous EGFR, and cytoplasmic EGFR were analyzed by immunohistochemistry using tissue microarray blocks made from surgical specimens. Results: Patients with high levels of membranous EGFR in tissue microarrays had significantly shorter overall survival (OS) and disease-free survival (DFS): high membranous EGFR (score 0–2) 38.0 months versus low membranous EGFR (score 3) 14.4 months (p=0.008) and high membranous EGFR (score 0–2) 23.2 months versus low membranous EGFR (score 3) 6.1 months (p=0.004), respectively. On the other hand, E-cadherin, Snail, cytoplasmic EGFR, and IL-6 did not show significant association with OS or DFS. Patients with distant metastasis had significantly higher IL-6 levels than those with locoregional recurrence (p=0.01). Conclusions: This study showed that overexpression of membranous EGFR was significantly associated with shorter OS and DFS in surgically resected bile duct cancer patients. In addition, higher IL-6 expression was a predictive marker for recurrence in cholangiocarcinoma patients with distant organ metastasis after surgical resection.

참고문헌 (49)

  1. Anderson CD, "Diagnosis and treatment of cholangiocarcinoma", Oncologist, 9, pp.43~57 (2004)
  2. Boris Blechacz, "Cholangiocarcinoma: Current Knowledge and New Developments", Gut and Liver, 11(1), pp.13~26 (2017), 거트앤리버 소화기연관학회협의회
  3. Sun Choon Song, "Survival benefits of surgical resection in recurrent cholangiocarcinoma", Annals of Surgical Treatment and Research, 81(3), pp.187~194 (2011), 대한외과학회
  4. Jarnagin WR, "Surgical management of cholangiocarcinoma", Semin Liver Dis, 24, pp.189~199 (2004)
  5. Nagorney DM, "Outcomes after curative resections of cholangiocarcinoma", Arch Surg, 128, pp.871~879 (1993)
  6. Khan AS, "Cholangiocarcinoma", Surg Clin North Am, 99, pp.315~335 (2019)
  7. Ruys AT, "Prognostic biomarkers in patients with resected cholangiocarcinoma : a systematic review and meta-analysis", Ann Surg Oncol, 21, pp.487~500 (2014)
  8. Yoshikawa D, "Clinicopathological and prognostic significance of EGFR, VEGF, and HER2expression in cholangiocarcinoma", Br J Cancer, 98, pp.418~425 (2008)
  9. Rizvi S, "Emerging molecular therapeutic targets for cholangiocarcinoma", J Hepatol, 67, pp.632~644 (2017)
  10. Yang X, "Characterization of EGFR family gene aberrations in cholangiocarcinoma", Oncol Rep, 32, pp.700~708 (2014)
  11. Wehbe H, "Interleukin-6 contributes to growth in cholangiocarcinoma cells by aberrant promoter methylation and gene expression", Cancer Res, 66, pp.10517~10524 (2006)
  12. Yamada D, "Role of crosstalk between interleukin-6 and transforming growth factor-beta 1 in epithelial-mesenchymal transition and chemoresistance in biliary tract cancer", Eur J Cancer, 49, pp.1725~1740 (2013)
  13. Vaquero J, "Epithelial-mesenchymal transition in cholangiocarcinoma : from clinical evidence to regulatory networks", J Hepatol, 66, pp.424~441 (2017)
  14. Kong D, "Prognostic significance of Snail expression in hilar cholangiocarcinoma", Braz J Med Biol Res, 45, pp.617~624 (2012)
  15. Kudo-Saito C, "Cancer metastasis is accelerated through immunosuppression during Snail-induced EMT of cancer cells", Cancer Cell, 15, pp.195~206 (2009)
  16. Nitta T, "Prognostic significance of epithelial-mesenchymal transition-related markers in extrahepatic cholangiocarcinoma : comprehensive immunohistochemical study using a tissue microarray", Br J Cancer, 111, pp.1363~1372 (2014)
  17. Onder TT, "Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways", Cancer Res, 68, pp.3645~3654 (2008)
  18. Techasen A, "Loss of E-cadherin promotes migration and invasion of cholangiocarcinoma cells and serves as a potential marker of metastasis", Tumour Biol, 35, pp.8645~8652 (2014)
  19. Vleminckx K, "Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role", Cell, 66, pp.107~119 (1991)
  20. Yao X, "Clinicopathological and prognostic significance of epithelial mesenchymal transition-related protein expression in intrahepatic cholangiocarcinoma", Onco Targets Ther, 5, pp.255~261 (2012)
  21. Fukase K, "Bile acids repress Ecadherin through the induction of Snail and increase cancer invasiveness in human hepatobiliary carcinoma", Cancer Sci, 99, pp.1785~1792 (2008)
  22. Sato Y, "Epithelial-mesenchymal transition induced by transforming growth factor-β1", Snail activation aggravates invasive growth of cholangiocarcinoma, 2010, pp.177, 141~152
  23. Patel T, "Cholangiocarcinoma : emerging approaches to a challenging cancer", Curr Opin Gastroenterol, 23, pp.317~323 (2007)
  24. Nguyen MLT, "Targeting interleukin 6 signaling by monoclonal antibody siltuximab on cholangiocarcinoma", J Gastroenterol Hepatol, 36, pp.1334~1345 (2021)
  25. 정영재, "Prognostic factors following surgical resection of distal bile duct cancer", Annals of Surgical Treatment and Research, 85(5), pp.212~218 (2013), 대한외과학회
  26. Lu Z, "Epidermal growth factor-induced tumor cell invasion and metastasis initiated by dephosphorylation and downregulation of focal adhesion kinase", Mol Cell Biol, 21, pp.4016~4031 (2001)
  27. Salomon DS, "Epidermal growth factor-related peptides and their receptors in human malignancies", Crit Rev Oncol Hematol, 19, pp.183~232 (1995)
  28. Chang YT, "Clinicopathological and prognostic significances of EGFR, KRAS and BRAF mutations in biliary tract carcinomas in Taiwan", J Gastroenterol Hepatol, 29, pp.1119~1125 (2014)
  29. Gwak GY, "Detection of responsepredicting mutations in the kinase domain of the epidermal growth factor receptor gene in cholangiocarcinomas", J Cancer Res Clin Oncol, 131, pp.649~652 (2005)
  30. Leone F, "Somatic mutations of epidermal growth factor receptor in bile duct and gallbladder carcinoma", Clin Cancer Res, 12, pp.1680~1685 (2006)
  31. Pu YS, "Characterization of membranous and cytoplasmic EGFR expression in human normal renal cortex and renal cell carcinoma", J Biomed Sci, 16, pp.82~ (2009)
  32. Kallio JP, "Membranous location of EGFR immunostaining is associated with good prognosis in renal cell carcinoma", Br J Cancer, 89, pp.1266~1269 (2003)
  33. Mahipal A, "Cell membrane and cytoplasmic epidermal growth factor receptor expression in pancreatic ductal adenocarcinoma", Med Oncol, 29, pp.134~139 (2012)
  34. Ueda S, "The correlation between cytoplasmic overexpression of epidermal growth factor receptor and tumor aggressiveness : poor prognosis in patients with pancreatic ductal adenocarcinoma", Pancreas, 29, pp.e1~e8 (2004)
  35. Akslen LA, "Prognostic impact of EGF-receptor in papillary thyroid carcinoma", Br J Cancer, 68, pp.808~812 (1993)
  36. Kappler M, "Prognostic impact of cytoplasmatic EGFR upregulation in patients with oral squamous cell carcinoma : a pilot study", Mol Clin Oncol, 13, pp.88~ (2020)
  37. Piyathilake CJ, "Differential expression of growth factors in squamous cell carcinoma and precancerous lesions of the lung", Clin Cancer Res, 8, pp.734~744 (2002)
  38. Bache KG, "Defective downregulation of receptor tyrosine kinases in cancer", EMBO J, 23, pp.2707~2712 (2004)
  39. Roepstorff K, "Endocytic downregulation of ErbB receptors : mechanisms and relevance in cancer", Histochem Cell Biol, 129, pp.563~578 (2008)
  40. Zhang M, "Expression of interleukin-6 is associated with epithelial-mesenchymal transition and survival rates in gallbladder cancer", Mol Med Rep, 11, pp.3539~3546 (2015)
  41. Goydos JS, "Marked elevation of serum interleukin-6 in patients with cholangiocarcinoma : validation of utility as a clinical marker", Ann Surg, 227, pp.398~404 (1998)
  42. Yokomuro S, "Growth control of human biliary epithelial cells by interleukin 6, hepatocyte growth factor, transforming growth factor beta1, and activin A : comparison of a cholangiocarcinoma cell line with primary cultures of non-neoplastic biliary epithelial cells", Hepatology, 32, pp.26~35 (2000)
  43. Camp RL, "Validation of tissue microarray technology in breast carcinoma", Lab Invest, 80, pp.1943~1949 (2000)
  44. Mills SE, "Guardians of the wax. . . and the patient", Am J Clin Pathol, 104, pp.365~367 (1995)
  45. Griffin MC, "Validation of tissue microarrays using p53 immunohistochemical studies of squamous cell carcinoma of the larynx", Mod Pathol, 16, pp.1181~1188 (2003)
  46. Rosen DG, "Validation of tissue microarray technology in ovarian carcinoma", Mod Pathol, 17, pp.790~797 (2004)
  47. Fernebro E, "Evaluation of the tissue microarray technique for immunohistochemical analysis in rectal cancer", Arch Pathol Lab Med, 126, pp.702~705 (2002)
  48. Kallioniemi OP, "Tissue microarray technology for high-throughput molecular profiling of cancer", Hum Mol Genet, 10, pp.657~662 (2001)
  49. Zerkowski MP, "Quantitative analysis of breast cancer tissue microarrays shows high cox-2 expression is associated with poor outcome", Cancer Invest, 25, pp.19~26 (2007)

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