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The Ability to Diagnose Intrahepatic Cholangiocarcinoma Definitively Using Novel Branched DNA-Enhanced Albumin RNA In Situ Hybridization Technology. Ann Surg Oncol 2016 Jan;23(1):290-6

Date

12/19/2014

Pubmed ID

25519926

Pubmed Central ID

PMC4472634

DOI

10.1245/s10434-014-4247-8

Scopus ID

2-s2.0-84952628800 (requires institutional sign-in at Scopus site)   81 Citations

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.

Author List

Ferrone CR, Ting DT, Shahid M, Konstantinidis IT, Sabbatino F, Goyal L, Rice-Stitt T, Mubeen A, Arora K, Bardeesey N, Miura J, Gamblin TC, Zhu AX, Borger D, Lillemoe KD, Rivera MN, Deshpande V

Author

Thomas Clark Gamblin MD Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Aged
Albumins
Bile Duct Neoplasms
Carcinoma, Hepatocellular
Cholangiocarcinoma
DNA
Female
Follow-Up Studies
Humans
In Situ Hybridization
Liver Neoplasms
Male
Neoplasm Grading
Prognosis
RNA, Messenger