Detection of Albumin Expression by RNA In Situ Hybridization Is a Sensitive and Specific Method for Identification of Hepatocellular Carcinomas and Intrahepatic Cholangiocarcinomas

Lin, Fan; Shi, Jianhui; Wang, Hanlin L.; Ma, Xiao‐Jun; Monroe, R. J.; Luo, Yuling; Chen, Zong-Ming; Liu, Haiyan

doi:10.1093/ajcp/aqy030

Cited by 30 publications

(18 citation statements)

References 26 publications

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“…Cholangiocarcinoma cell arising from cell proliferation after bile duct injury could be a form of undifferenciated cholangiocyte producing albumin. There are several reports on aberrant expression of albumin; it could be used to distinguish bile duct neoplasm from other metastatic adenocarcinoma [46][47][48].…”

Section: Discussionmentioning

confidence: 99%

Quantitative proteomic analysis of bile in extrahepatic cholangiocarcinoma patients

et al. 2020

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Background and Aims: Extrahepatic cholangiocarcinoma (CCA) without liver-fluke is increasing. Multifactorial carcinogenesis makes it hard to find biomarkers related to CCA. Although there are a few studies of bile proteomics, these showed different protein profiles because of having heterogeneous groups of patients and different sampling methods. Our aim was to identify the specific bile proteins of extrahepatic CCA patients. Methods: We collected bile from 23 patients undergoing endoscopic nasobiliary drainage in Korea University Guro Hospital from May 2018 to January 2019. The CCA group included 18 patients diagnosed with extrahepatic CCA, and the control group included 5 patients with benign biliary conditions. We analyzed bile proteome using liquid chromatography mass spectrometry. We compared the relative abundance of various proteins in the CCA and control groups. Results: In all, we identified a total of 245 proteins in the bile of CCA and control patients. Increased top 14 proteins in CCA patients were immunoglobulin kappa light chain, apolipoprotein B, inter-alpha-trypsin inhibitor heavy chain H4, apolipoprotein E, Mucin 5B, inter-alpha-trypsin inhibitor heavy chain H1, apolipoprotein A-IV, intercellular adhesion molecule 1, complement C7, complement C5, apolipoprotein C-III, albumin, antithrombin-III, and apolipoprotein A-II. However, the significantly increased proteins in bile of CCA patients comparing with control patients were immunoglobulin kappa light chain, apolipoprotein E, albumin, apolipoprotein A-I, antithrombin-III, α1-antitrypsin, serotransferrin, immunoglobulin heavy constant mu, immunoglobulin J chain, complement C4-A, and complement C3 (p<0.05). Conclusions: In this study, we identified several proteins that were significantly increased in the bile of extrahepatic CCA. Further study is needed to validate them as potential tumor-associated proteins that may be potential biomarkers for CCA.

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Section: Discussionmentioning

confidence: 99%

Quantitative proteomic analysis of bile in extrahepatic cholangiocarcinoma patients

et al. 2020

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“…It should be noted that unlike the current study, this analysis was performed on tissue microarrays composed of 0.1 cm cores of tissue, and given the heterogeneity in expression, these samples may not have been adequate to assess albumin expression 16. In another study, albumin reactivity was noted in 36 of 37 (97%) HCCs and 14 of 22 (64%) ICCs 17. The authors also evaluated breast carcinomas, and adenocarcinomas from the lung, oesophagus, pancreas, bladder, endometrium, endocervix, ovary, kidney, as well as mesotheliomas, and papillary thyroid carcinomas.…”

Section: Discussionmentioning

confidence: 83%

“…This study was performed using a manual platform and not an automated assay as performed in this study 17. Additionally, the authors did not specify the age of the paraffin blocks in these studies 16 17. We have noticed significant degradation in RNA quantity in blocks older than a decade, as evidenced by the significantly lower sensitivity (25%) in our retrospective biopsy cohort.…”

Section: Discussionmentioning

confidence: 85%

“…The authors also evaluated breast carcinomas, and adenocarcinomas from the lung, oesophagus, pancreas, bladder, endometrium, endocervix, ovary, kidney, as well as mesotheliomas, and papillary thyroid carcinomas. With the exception of a case of lung adenocarcinoma, the 454 non-hepatic tumours were negative for albumin 17. This study was performed using a manual platform and not an automated assay as performed in this study 17.…”

Section: Discussionmentioning

confidence: 99%

“…With the exception of a case of lung adenocarcinoma, the 454 non-hepatic tumours were negative for albumin 17. This study was performed using a manual platform and not an automated assay as performed in this study 17. Additionally, the authors did not specify the age of the paraffin blocks in these studies 16 17.…”

Section: Discussionmentioning

confidence: 99%

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Cholangiolar pattern and albumin in situ hybridisation enable a diagnosis of intrahepatic cholangiocarcinoma

et al. 2019

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AimsThe histological distinction of intrahepatic cholangiocarcinoma (ICC) from metastatic adenocarcinoma remains a challenge. The primary goal was to evaluate the diagnostic value of morphology and albumin expression in the diagnosis of ICC.MethodsWe evaluated morphological patterns in 120 ICCs and 677 non-hepatic adenocarcinomas and performed in situ hybridisation (ISH) stain for albumin in the former cohort (retrospective cohort). We also identified 119 samples from primary and metastatic lesions, the validation cohort, in which albumin ISH was performed as part of the diagnostic workup. Targeted sequencing was performed on selected cases. We also mined existing expression profiling data including cases from The Cancer Genome Atlas (TCGA) (41 760 unique samples).ResultsIn the retrospective cohort, 45% of ICCs and <1% of non-hepatic adenocarcinomas showed a cholangiolar pattern; albumin ISH was positive in 93% of ICCs with significant intratumorous heterogeneity. In the validation cohort, 29% of ICCs showed a cholangiolar pattern and 88% expressed albumin, while all metastatic non-hepatic neoplasms were negative (n=37) (sensitivity 88% and specificity 100%). Targetable genetic alterations (IDH mutations and FGFR2 fusions) were identified in 31% of ICCs (10 of 32). An analysis of the TCGA data validated the specificity of the albumin assay.ConclusionsThe cholangiolar pattern and albumin RNA ISH distinguishes ICC from metastatic adenocarcinoma with high specificity. Given the high prevalence of targetable mutations in ICC, albumin RNA ISH is an essential component in the workup of tumours of uncertain origin. A specific diagnosis of ICC could trigger molecular testing and uncover targetable genetic alterations.

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Pathological Diagnosis of Cholangiocarcinoma

Sigel

Wang

2021

Diagnosis and Management of Cholangiocarcinoma

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Detection of Albumin Expression by RNA In Situ Hybridization Is a Sensitive and Specific Method for Identification of Hepatocellular Carcinomas and Intrahepatic Cholangiocarcinomas

Abstract: RNAscope for albumin is highly sensitive and specific for identifying HCCs and is highly specific and moderately sensitive for detection of ICCs; however, rare carcinomas (non-HCC, non-ICC, and those with no hepatoid histomorphology) can also have aberrant expression of albumin.

Cited by 30 publications

References 26 publications

Quantitative proteomic analysis of bile in extrahepatic cholangiocarcinoma patients

Quantitative proteomic analysis of bile in extrahepatic cholangiocarcinoma patients

Cholangiolar pattern and albumin in situ hybridisation enable a diagnosis of intrahepatic cholangiocarcinoma

Pathological Diagnosis of Cholangiocarcinoma

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