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

Gut Liver. 2023 Jan 15;17(1):159-169. doi: 10.5009/gnl220044. Epub 2022 Nov 1.

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.

Keywords: Cholangiocarcinoma; Immunohistochemistry; Microarray; Prognosis.

MeSH terms

  • Bile Duct Neoplasms* / surgery
  • Bile Ducts, Intrahepatic
  • Cadherins / analysis
  • Cadherins / metabolism
  • Cholangiocarcinoma* / surgery
  • ErbB Receptors / analysis
  • ErbB Receptors / metabolism
  • Humans
  • Immunoassay
  • Interleukin-6 / metabolism
  • Neoplasm Recurrence, Local / metabolism
  • Prognosis

Substances

  • Interleukin-6
  • Cadherins
  • ErbB Receptors