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Combined analysis of albumin in situ hybridisation and C reactive protein immunohistochemistry for the diagnosis of intrahepatic cholangiocarcinoma: towards a molecular classification paradigm

Aims Intrahepatic cholangiocarcinoma (iCCA) is a diagnosis of exclusion that can pose a challenge to the pathologist despite thorough clinical workup. Although several immunohistochemical markers have been proposed for iCCA, none of them reached clinical practice. We here assessed the combined usage...

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Hauptverfasser: Albrecht, Thomas (VerfasserIn) , Rossberg, Annik (VerfasserIn) , Rose, Fabian (VerfasserIn) , Breuhahn, Kai (VerfasserIn) , Baumann, Eva-Marie (VerfasserIn) , Tóth, Marcell (VerfasserIn) , Brinkmann, Fritz (VerfasserIn) , Charbel, Alphonse (VerfasserIn) , Vogel, Monika Nadja (VerfasserIn) , Köhler, Bruno Christian (VerfasserIn) , Mehrabi, Arianeb (VerfasserIn) , Büchler, Markus W. (VerfasserIn) , Singer, Stephan (VerfasserIn) , Solass, Wiebke (VerfasserIn) , Straub, Beate (VerfasserIn) , Schirmacher, Peter (VerfasserIn) , Rössler, Stephanie (VerfasserIn) , Goeppert, Benjamin (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2025
In: Journal of clinical pathology
Year: 2025, Jahrgang: 78, Heft: 5, Pages: 307-316
ISSN:1472-4146
DOI:10.1136/jcp-2024-209429
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1136/jcp-2024-209429
Verlag, kostenfrei, Volltext: https://jcp.bmj.com/content/early/2024/05/14/jcp-2024-209429
Volltext
Verfasserangaben:Thomas Albrecht, Annik Rossberg, Fabian Rose, Kai Breuhahn, Eva-Marie Baumann, Marcell Tóth, Fritz Brinkmann, Alphonse Charbel, Monika Nadja Vogel, Bruno Köhler, Arianeb Mehrabi, Markus Wolfgang Büchler, Stephan Singer, Wiebke Solass, Beate Straub, Peter Schirmacher, Stephanie Roessler, Benjamin Goeppert
Beschreibung
Zusammenfassung:Aims Intrahepatic cholangiocarcinoma (iCCA) is a diagnosis of exclusion that can pose a challenge to the pathologist despite thorough clinical workup. Although several immunohistochemical markers have been proposed for iCCA, none of them reached clinical practice. We here assessed the combined usage of two promising diagnostic approaches, albumin in situ hybridisation (Alb-ISH) and C reactive protein (CRP) immunohistochemistry, for distinguishing iCCA from other adenocarcinoma primaries. - Methods We conducted Alb-ISH and CRP immunohistochemistry in a large European iCCA cohort (n=153) and compared the results with a spectrum of other glandular adenocarcinomas of different origin (n=885). In addition, we correlated expression patterns with clinicopathological information and mutation data. - Results Alb-ISH was highly specific for iCCA (specificity 98.8%) with almost complete negativity in perihilar CCA and only rare positives among other adenocarcinomas (sensitivity 69.5%). CRP identified the vast majority of iCCA cases (sensitivity 84.1%) at a lower specificity of 86.4%. Strikingly, the combination of CRP and Alb-ISH boosted the diagnostic sensitivity to 88.0% while retaining a considerable specificity of 86.1%. Alb-ISH significantly correlated with CRP expression, specific tumour morphologies and small or large duct iCCA subtypes. Neither Alb-ISH nor CRP was associated with iCCA patient survival. 16 of 17 recurrent mutations in either IDH1, IDH2 and FGFR2 affected Alb-ISH positive cases, while the only KRAS mutation corresponded to an Alb-ISH negative case. - Conclusions In conclusion, we propose a sequential diagnostic approach for iCCA, integrating CRP immunohistochemistry and Alb-ISH. This may improve the accuracy of CCA classification and pave the way towards a molecular-guided CCA classification.
Beschreibung:Online veröffentlicht: 15 May 2024
Gesehen am 09.12.2024
Beschreibung:Online Resource
ISSN:1472-4146
DOI:10.1136/jcp-2024-209429

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