scholarly journals α-Fetoprotein mRNA in situ hybridisation is a highly specific marker of hepatocellular carcinoma: a multi-centre study

Author(s):  
Shi-Xun Lu ◽  
Yu-Hua Huang ◽  
Li-Li Liu ◽  
Chris Zhiyi Zhang ◽  
Xia Yang ◽  
...  

Abstract Background Pathologic diagnosis of hepatocellular carcinoma (HCC) can be challenging in differentiating from benign and non-hepatocytic malignancy lesions. The aim of this study was to investigate the potential utility of α-fetoprotein (AFP) mRNA RNAscope, a sensitive and specific method, in the diagnosis of HCC. Methods Three independent retrospective cohorts containing 2216 patients with HCC, benign liver lesions, and non-hepatocytic tumours were examined. AFP was detected using ELISA, IHC (Immunohistochemistry), and RNAscope. Glypican3 (GPC3), hepatocyte paraffin-1 (HepPar-1), and arginase-1 (Arg-1) proteins were detected using IHC. Results AFP RNAscope improved the HCC detection sensitivity by 24.7–32.7% compared with IHC. In two surgical cohorts, a panel of AFP RNAscope and GPC3 provided the best diagnostic value in differentiating HCC from benign hepatocytic lesions (AUC = 0.905 and 0.811), and a panel including AFP RNAscope, GPC3, HepPar-1, and Arg-1 yielded the best AUC (0.971 and 0.977) when distinguishing HCC from non-hepatocytic malignancies. The results from the liver biopsy cohort were similar, and additional application of AFP RNAscope improved the sensitivity by 18% when distinguishing HCC from benign hepatocytic lesions. Conclusions AFP mRNA detected by RNAscope is highly specific for hepatocytic malignancy and may serve as a novel diagnostic biomarker for HCC.

1997 ◽  
Vol 50 (5) ◽  
pp. 442-444 ◽  
Author(s):  
M R Stephen ◽  
K Oien ◽  
R K Ferrier ◽  
R A Burnett

2008 ◽  
Vol 14 (4) ◽  
pp. 213-219 ◽  
Author(s):  
Francesco Negro ◽  
Mauro Papotti ◽  
Donatella Pacchioni ◽  
Francesco Galimi ◽  
Ferruccio Bonino ◽  
...  

2020 ◽  
pp. jclinpath-2020-206663
Author(s):  
Diane Ann Chen ◽  
Anne Koehne de Gonzalez ◽  
Ladan Fazlollahi ◽  
Amy Coffey ◽  
Helen E. Remotti ◽  
...  

AimsIn situ hybridisation (ISH) for albumin mRNA is a sensitive marker of primary liver tumours in adults. However, paediatric tumours, such as hepatoblastoma (HB) and fibrolamellar hepatocellular carcinoma (FLC), have not been tested thoroughly and may require ancillary tests to diagnose with confidence. We aim to determine if albumin ISH is useful in the pathological evaluation of these malignancies and to compare it to commonly used immunohistochemical markers HepPar 1 (HEPA) and arginase-1 (ARG).MethodsTissue microarrays of 26 HB and 10 FLC were constructed. Controls included 4 embryonal undifferentiated sarcomas of the liver, 51 neuroblastomas and 64 Wilms tumours. We evaluated a commercially available RNA ISH to detect albumin mRNA. Immunohistochemistry for HEPA and ARG was performed in the usual fashion.ResultsTwenty-six of 26 HB showed positive staining by albumin ISH including 14 fetal, 8 embryonal and 4 mixed variants. All 10 FLC were diffusely positive. The sensitivity and specificity of albumin ISH were 100% for HB and FLC. ARG had 100% sensitivity and specificity for HB (26 of 26 cases) and FLC (9 of 9). HEPA stained 22 of 26 HB (85% sensitivity, 99.2% specificity) and 7 of 9 FLC (78% sensitivity, 99.1% specificity).ConclusionAlbumin RNA ISH is a useful test to determine hepatocytic origin in HB and FLC. ARG was equally sensitive and easy to interpret, while HEPA was inferior to both in HB and FLC.


2017 ◽  
Vol 71 (3) ◽  
pp. 221-227 ◽  
Author(s):  
Kshitij Arora ◽  
Munita Bal ◽  
Angela Shih ◽  
Andrea Moy ◽  
Lawerence Zukerberg ◽  
...  

AimsThis multi-institutional study and a re-evaluation of the TCGA cohort explores the morphological spectrum, genetics and outcome of GI (gastrointestinal) hepatoid tumours, tumours expressing alpha-fetoprotein (AFP) and fetal-type (FT) GI adenocarcinomas.Methods44 tumours with evidence of hepatocellular differentiation were evaluated for morphology as well as by immunohistochemistry for AFP, HepPar1, glypican-3 and arginase-1 and by in situ hybridisation for albumin. Three categories were defined: type I (hepatoid: morphological evidence of hepatocellular differentiation), type II (FT GI adenocarcinoma: tubular profiles and subnuclear vacuolisation, resembling fetal intestine) and type III: positive for at least two hepatocyte-specific markers but lacking morphological evidence of hepatocellular differentiation. GI adenocarcinomas in the TCGA cohort were also evaluated (n=829).Results18 cases were classified as type I, 19 as FT GI adenocarcinomas and 7 as type III (resembling conventional gastrointestinal carcinomas). Serum AFP was elevated in 92% of cases. 93% of tumours were positive for glypican-3, 90% for albumin and 89% for AFP. Arginase-1 was restricted to 35% of type 1 tumours. TCGA gastric tumours with elevated AFP expression showed morphological features of FT GI adenocarcinoma (70%) and were exclusively MSI stable. TCGA gastric adenocarcinomas with high AFP expression showed inferior survival on univariate and multivariate analysis.ConclusionsFT GI adenocarcinomas show a distinctive morphological and immunohistochemical profile. Gastric adenocarcinomas with elevated expression of AFP morphologically resemble FT GI adenocarcinomas, demonstrate aggressive behaviour, independent of grade and stage, and a distinct genetic profile.


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