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In situ hybridisation for albumin RNA in paediatric liver cancers compared with common immunohistochemical markers
  1. Diane Ann Chen1,
  2. Anne Koehne de Gonzalez1,
  3. Ladan Fazlollahi1,
  4. Amy Coffey2,
  5. Helen E. Remotti1,
  6. Stephen M. Lagana1
  1. 1 Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA
  2. 2 Department of Diagnostic Medicine, University of Texas System, Austin, Texas, USA
  1. Correspondence to Dr Stephen M. Lagana, Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA; sml2179{at}


Aims In 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).

Methods Tissue 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.

Results Twenty-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).

Conclusion Albumin 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.

  • liver neoplasms
  • pediatrics
  • in situ hybridisation

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  • Handling editor Runjan Chetty.

  • DAC and AKdG contributed equally.

  • Contributors SML conceived of the presented idea. The TMAs were constructed by HR and AC. Histological interpretation was performed by HR, SML and AKdG. DAC, AKdG and SML wrote the manuscript with input from all authors. The project was supervised by SML, HR and LF. All authors provided critical feedback and helped shape the research, analysis and manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as online supplementary information. All data are summarised in included tables. Source files without patient identifiers could be shared on reasonable request to the corresponding author.