Annals of Surgical Oncology

, Volume 23, Issue 1, pp 290–296 | Cite as

The Ability to Diagnose Intrahepatic Cholangiocarcinoma Definitively Using Novel Branched DNA-Enhanced Albumin RNA In Situ Hybridization Technology

  • Cristina R. Ferrone
  • David T. Ting
  • Mohammed Shahid
  • Ioannis T. Konstantinidis
  • Francesco Sabbatino
  • Lipika Goyal
  • Travis Rice-Stitt
  • Ayesha Mubeen
  • Kshitij Arora
  • Nabeel Bardeesey
  • John Miura
  • T. Clark Gamblin
  • Andrew X. Zhu
  • Darrell Borger
  • Keith D. Lillemoe
  • Miguel N. Rivera
  • Vikram Deshpande
Translational Research and Biomarkers

Abstract

Background

Intrahepatic cholangiocarcinoma (ICC) often is a diagnosis determined by exclusion. Distinguishing ICC from other metastatic adenocarcinomas based on histopathologic or immunohistochemical analysis often is difficult and requires an extensive workup. This study aimed to determine whether albumin, whose expression is restricted to the liver, has potential as a biomarker for ICC using a novel and highly sensitive RNA in situ hybridization (ISH) platform.

Methods

Modified branched DNA probes were developed for albumin RNA ISH. The study evaluated 467 patient samples of primary and metastatic lesions.

Results

Of the 467 samples evaluated, 83 were ICCs, 42 were hepatocellular carcinomas (HCCs), and 332 were nonhepatic carcinomas including tumors arising from the perihilar region and bile duct, pancreas, stomach, esophagus, colon, breast, ovary, endometrium, kidney, and urinary bladder. Albumin RNA ISH was highly sensitive for cancers of liver origin, staining positive in 82 (99 %) of 83 ICCs and in 42 HCCs (100 %). Perihilar and distal bile duct carcinomas as well as carcinomas arising at other sites tested negative for albumin. Notably, 6 (22 %) of 27 intrahepatic tumors previously diagnosed as carcinomas of undetermined origin tested positive for albumin.

Conclusions

Albumin RNA ISH is a sensitive and highly specific diagnostic tool for distinguishing ICC from metastatic adenocarcinoma to the liver or carcinoma of unknown origin. Albumin RNA ISH could replace the extensive diagnostic workup, leading to timely confirmation of the ICC diagnosis. Additionally, the assay could serve as a guide to distinguish ICC from perihilar adenocarcinoma.

Supplementary material

10434_2014_4247_MOESM1_ESM.docx (14 kb)
Supplementary material 1 (DOCX 14 kb)
10434_2014_4247_MOESM2_ESM.xlsx (13 kb)
Supplementary material 2 (XLSX 13 kb)

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Copyright information

© Society of Surgical Oncology 2014

Authors and Affiliations

  • Cristina R. Ferrone
    • 1
  • David T. Ting
    • 2
  • Mohammed Shahid
    • 1
    • 3
  • Ioannis T. Konstantinidis
    • 1
  • Francesco Sabbatino
    • 1
  • Lipika Goyal
    • 2
  • Travis Rice-Stitt
    • 3
  • Ayesha Mubeen
    • 1
  • Kshitij Arora
    • 1
    • 3
  • Nabeel Bardeesey
    • 2
  • John Miura
    • 4
  • T. Clark Gamblin
    • 4
  • Andrew X. Zhu
    • 2
  • Darrell Borger
    • 1
  • Keith D. Lillemoe
    • 1
  • Miguel N. Rivera
    • 3
  • Vikram Deshpande
    • 3
  1. 1.Department of SurgeryMassachusetts General HospitalBostonUSA
  2. 2.Division of Hematology/Oncology, Department of MedicineMassachusetts General HospitalBostonUSA
  3. 3.Division of PathologyMassachusetts General HospitalBostonUSA
  4. 4.Division of Surgical OncologyMedical College of WisconsinMilwaukeeUSA

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