Nestin as a diagnostic and prognostic marker for combined hepatocellular-cholangiocarcinoma

Caldéraro, Julien; Tommaso, Luca Di; Maillé, Pascale; Beaufrère, Aurélie; Nguyễn, Công Trung; Heij, Lara; Gnemmi, Viviane; Graham, Rondell P.; Charlotte, Frédéric; Chartier, Suzanne; Wendum, Dominique; Vij, Mukul; Allende, Daniela S.; Díaz, Alba; Fuster, Carla; Rivière, Benjamin; Herrero, Astrid; Evert, Katja; Calvisi, Diego F.; Leow, Wei Qiang; Leung, Howard H W; Bednarsch, Jan; Boleslawski, Emmanuel; Rela, Mohamed; Chan, Anthony Wing–Hung; Forner, Alejandro; Reig, María; Pujals, Anaïs; Favre, Loëtitia; Allaire, Manon; Scatton, Olivier; Uguen, Arnaud; Trépo, Eric; Sanchez, Lukas Otero; Chatelain, Denis; Remmelink, Myriam; Boulagnon-Rombi, Camille; Bazille, Céline; Stürm, Nathalie; Menahem, Benjamin; Frouin, Éric; Tougeron, David; Tournigand, Christophe; Kempf, Emmanuelle; Kim, Haeryoung; Ningarhari, Massih; Michalak-Provost, S.; Kather, Jakob Nikolas; Gouw, Annette S.H.; Gopal, Purva; Brustia, Raffaele; Vibert, Éric; Schulze, Kornelius; Ruether, Darius Ferenc; Weidemann, Sören; Rhaiem, Rami; Nault, Jean‐Charles; Laurent, Alexis; Amaddeo, Giuliana; Regnault, Hélène; Martin, Eléonora De; Sempoux, Christine; Navale, Pooja; Shinde, Jayendra; Bacchuwar, Ketan; Westerhoff, Maria; Lo, Regina Cheuk‐Lam; Sebbagh, Mylène; Guettier, Catherine; Lequoy, Marie; Komuta, Mina; Ziol, Marianne; Paradis, Valérie; Shen, Jeanne; Caruso, Stefano

doi:10.1016/j.jhep.2022.07.019

Cited by 20 publications

(26 citation statements)

References 26 publications

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“…4 A recent multicenter study reported immunohistochemical nestin positivity as a diagnostic marker in typically combined hepatocellular-cholangiocarcinoma. 7 That study also demonstrated that nestin-high (> 30% neoplastic cells with positive immunostaining) combined hepatocellular-cholangiocarcinoma were associated with poor clinical outcomes even after surgical resection or liver transplantation. In the current report nestin, was completely negative again highlighting the unique nature of the tumor.…”

Section: Discussionmentioning

confidence: 75%

Biphenotypic Immunohistochemical Features and NTRK1 Amplification in Intermediate Cell Carcinoma of the Liver

Radhakrishnan

Martin

Vij³

et al. 2022

Int J Surg Pathol

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Intermediate cell carcinoma is one of the rarest forms of primary liver cancer comprising relatively monomorphic populations of neoplastic epithelial cells demonstrating simultaneous positivity of both hepatocyte and cholangiocyte immunohistochemical markers. Here in, we describe an adult male patient who underwent left hepatectomy for a large liver tumor. The pathological and immunohistochemical analysis revealed the malignant primary liver cancer with intermediate cell morphology and mixed immunophenotypic features consistent with intermediate cell carcinoma. Furthermore, the genomic profiling using the Next-generation sequencing (NGS) platform demonstrated that there is a novel amplification with copy number gain 12 (12 gene copies) in the Neurotrophic Receptor Tyrosine Kinase 1 ( NTRK1) gene, being an oncogenic driver of intermediate cell carcinoma. This is the first case report with the amplification in NTRK1 and emphasizes the importance of molecular oncology.

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Section: Discussionmentioning

confidence: 75%

Biphenotypic Immunohistochemical Features and NTRK1 Amplification in Intermediate Cell Carcinoma of the Liver

Radhakrishnan

Martin

Vij³

et al. 2022

Int J Surg Pathol

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“…The liver is the largest immune organ that has typical immune tolerance characteristics 17 . HCC has become the leading cause of cancer-related deaths in the world 18 . It has a complex ecosystem featured by high heterogeneity 19 .…”

Section: Discussionmentioning

confidence: 99%

NK cell marker gene-based model shows good predictive ability in prognosis and response to immunotherapies in hepatocellular carcinoma

et al. 2023

Sci Rep

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Hepatocellular carcinoma (HCC) is the fourth leading cause of malignancy worldwide, and its progression is influenced by the immune microenvironment. Natural killer (NK) cells are essential in the anti-tumor response and have been linked to immunotherapies for cancers. Therefore, it is important to unify and validate the role of NK cell-related gene signatures in HCC. In this study, we used RNA-seq analysis on HCC samples from public databases. We applied the ConsensusClusterPlus tool to construct the consensus matrix and cluster the samples based on their NK cell-related expression profile data. We employed the least absolute shrinkage and selection operator regression analysis to identify the hub genes. Additionally, we utilized the CIBERSORT and ESTIMATE web-based methods to perform immune-related evaluations. Our results showed that the NK cell-related gene-based classification divided HCC patients into three clusters. The C3 cluster was activated in immune activation signaling pathways and showed better prognosis and good clinical features. In contrast, the C1 cluster was remarkably enriched in cell cycle pathways. The stromal score, immune score, and ESTIMATE score in C3 were much higher than those in C2 and C1. Furthermore, we identified six hub genes: CDC20, HMOX1, S100A9, CFHR3, PCN1, and GZMA. The NK cell-related genes-based risk score subgroups demonstrated that a higher risk score subgroup showed poorer prognosis. In summary, our findings suggest that NK cell-related genes play an essential role in HCC prognosis prediction and have therapeutic potential in promoting NK cell antitumor immunity. The six identified hub genes may serve as useful biomarkers for novel therapeutic targets.

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“…To support the morphological diagnosis, some additional immunohistochemical (IHC) markers reflecting cell differentiation (hepatocytic and cholangiocytic) as well as stem cell phenotype are used; these latter are useful to better characterize PLC and to guide differential diagnoses without being diagnostic by themselves [ 2 , 3 , 4 ]. Recently, Nestin, a marker for cHCC-CCA, has also been reported to have prognostic value [ 5 ]. In the field of liver oncogenesis, cHCC-CCA illustrates the best example of morphological intratumor heterogeneity.…”

Section: Introductionmentioning

confidence: 99%

MALDI Imaging, a Powerful Multiplex Approach to Decipher Intratumoral Heterogeneity: Combined Hepato-Cholangiocarcinomas as Proof of Concept

Gigante

Cazier

Albuquerque

et al. 2023

Cancers

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Combined hepato-cholangiocarcinomas (cHCC-CCA) belong to the spectrum of primary liver carcinomas, which include hepatocellular carcinomas (HCC) and intrahepatic cholangiocarcinomas (iCCA) at both ends of the spectrum. Mainly due to the high intratumor heterogeneity of cHCC-CCA, its diagnosis and pathological description remain challenging. Taking advantage of in situ non-targeted molecular mapping provided by MALDI (Matrix Assisted Laser Desorption Ionization) imaging, we sought to develop a multiscale and multiparametric morphological approach, integrating molecular and conventional pathological analysis. MALDI imaging was applied to five representative cases of resected cHCC-CCA. Principal component analysis and segmentations with MALDI imaging techniques identified areas related to either iCCA or HCC and also hidden tumor areas not visible microscopically. In addition, the overlap between MALDI segmentation and immunostaining provided a comprehensive description of cHCC-CCA tumor heterogeneity by identifying transitional and micro-metastatic areas. Moreover, a list of peptides derived from in silico digestion was obtained for each immunohistochemical marker and was matched within the peptide peak list acquired by MALDI. Comparison of immunostaining images with ions from in silico digestion revealed an accurate identification of iCCA and HCC areas. Our study provides further evidence on the performance of MALDI imaging in exploring intratumor heterogeneity and offering virtual multiplex immunostaining through a single acquisition.

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Nestin as a diagnostic and prognostic marker for combined hepatocellular-cholangiocarcinoma

Cited by 20 publications

References 26 publications

Biphenotypic Immunohistochemical Features and NTRK1 Amplification in Intermediate Cell Carcinoma of the Liver

Biphenotypic Immunohistochemical Features and NTRK1 Amplification in Intermediate Cell Carcinoma of the Liver

NK cell marker gene-based model shows good predictive ability in prognosis and response to immunotherapies in hepatocellular carcinoma

MALDI Imaging, a Powerful Multiplex Approach to Decipher Intratumoral Heterogeneity: Combined Hepato-Cholangiocarcinomas as Proof of Concept

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