Decreasing Albumin mRNA Expression in Cholangiocarcinomas along the Bile Duct Tree

Pathobiology. 2024;91(5):338-344. doi: 10.1159/000538706. Epub 2024 May 19.

Abstract

Introduction: The progressive technologies in albumin in situ hybridization (ISH) changed the routine application and the differential diagnosis of hepatic malignancies in the last years. The aim of the present work was to assess the diagnostic utility of albumin ISH on different cholangiocarcinoma (CCA) subtypes, as well as to assess how albumin production changes along the biliary tree.

Methods: Forty-five CCAs were retrospectively selected: 29 intrahepatic (15 small-duct and 14 large-duct subtypes), 7 perihilar, and 9 extrahepatic. Histology was revised in all cases, and albumin ISH was automatically performed by the RNAscope®.

Results: ISH was always negative in extrahepatic CCAs, only 1 perihilar case was positive, and any positivity was observed in 25/29 (86.2%) intrahepatic CCAs (p < 0.001). Concerning CCA subtypes, mean cell positivity was 38.8 ± 29.8% in small-duct CCAs and 11.4 ± 21.9 in large-duct CCAs, respectively (p = 0.003); 12/15 (80.0%) small-duct and 3/14 (21.4%) large-duct CCAs showed >5% positive cells (p = 0.002; odds ratio 14.7).

Conclusions: The introduction of more sensitive techniques changed the indications for ISH since most small-duct intrahepatic CCAs show diffuse positivity. Albumin positivity decreases from liver periphery to the large ducts, suggesting that ISH can be helpful in the differential diagnosis between small-duct and large-duct CCAs, as well as between intrahepatic large-duct CCAs and metastases.

Keywords: Albumin; Bile ducts; Cholangiocarcinoma; In situ hybridization; mRNA.

MeSH terms

  • Adult
  • Aged
  • Albumins / metabolism
  • Bile Duct Neoplasms* / diagnosis
  • Bile Duct Neoplasms* / genetics
  • Bile Duct Neoplasms* / pathology
  • Bile Ducts / pathology
  • Bile Ducts, Intrahepatic / pathology
  • Biomarkers, Tumor / genetics
  • Cholangiocarcinoma* / diagnosis
  • Cholangiocarcinoma* / genetics
  • Cholangiocarcinoma* / pathology
  • Diagnosis, Differential
  • Female
  • Humans
  • In Situ Hybridization*
  • Male
  • Middle Aged
  • RNA, Messenger* / genetics
  • Retrospective Studies

Substances

  • RNA, Messenger
  • Albumins
  • Biomarkers, Tumor

Grants and funding

The work reported in this publication was funded by the Italian Ministry of Health, RC-2023-2778858 project.