%0 Journal Article %1 Calderaro2022-ci %A Calderaro, Julien %A Di Tommaso, Luca %A Maillé, Pascale %A Beaufrère, Aurélie %A Nguyen, Cong Trung %A Heij, Lara %A Gnemmi, Viviane %A Graham, Rondell P %A Charlotte, Frédéric %A Chartier, Suzanne %A Wendum, Dominique %A Vij, Mukul %A Allende, Daniela %A Diaz, Alba %A Fuster, Carla %A Rivière, Benjamin %A Herrero, Astrid %A Augustin, Jérémy %A Evert, Katja %A Calvisi, Diego Francesco %A Leow, Wei Qiang %A Leung, Howard Ho Wai %A Bednarsch, Jan %A Boleslawski, Emmanuel %A Rela, Mohamed %A Chan, Anthony Wing-Hung %A Forner, Alejandro %A Reig, Maria %A Pujals, Ana\"ıs %A Favre, Loetitia %A Allaire, Manon %A Scatton, Olivier %A Uguen, Arnaud %A Trépo, Eric %A Sanchez, Lukas Otero %A Chatelain, Denis %A Remmelink, Myriam %A Boulagnon-Rombi, Camille %A Bazille, Céline %A Sturm, Nathalie %A Menahem, Benjamin %A Frouin, Eric %A Tougeron, David %A Tournigand, Christophe %A Kempf, Emmanuelle %A Kim, Haeryoung %A Ningarhari, Massih %A Michalak-Provost, Sophie %A Kather, Jakob Nikolas %A Gouw, Annette S H %A Gopal, Purva %A Brustia, Raffaele %A Vibert, Eric %A Schulze, Kornelius %A Rüther, Darius F %A Weidemann, Sören A %A Rhaiem, Rami %A Nault, Jean-Charles %A Laurent, Alexis %A Amaddeo, Giuliana %A Regnault, Hélène %A de Martin, Eleonora %A Sempoux, Christine %A Navale, Pooja %A Shinde, Jayendra %A Bacchuwar, Ketan %A Westerhoff, Maria %A Lo, Regina Cheuk-Lam %A Sebbagh, Mylène %A Guettier, Catherine %A Lequoy, Marie %A Komuta, Mina %A Ziol, Marianne %A Paradis, Valérie %A Shen, Jeanne %A Caruso, Stefano %D 2022 %I Elsevier BV %J J. Hepatol. %K cancer; carcinoma; cholangiocarcinoma; combined hepatocellular hepatocellular-cholangiocarcinoma; liver; nestin %N 6 %P 1586--1597 %T Nestin as a diagnostic and prognostic marker for combined hepatocellular-cholangiocarcinoma %V 77 %X BACKGROUND & AIMS: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer (PLC) associated with a poor prognosis. Given the challenges in its identification and its clinical implications, biomarkers are critically needed. We aimed to investigate the diagnostic and prognostic value of the immunohistochemical expression of Nestin, a progenitor cell marker, in a large multicentric series of PLCs. METHODS: We collected 461 cHCC-CCA samples from 32 different clinical centers. Control cases included 368 hepatocellular carcinomas (HCCs) and 221 intrahepatic cholangiocarcinomas (iCCAs). Nestin immunohistochemistry was performed on whole tumor sections. Diagnostic and prognostic performances of Nestin expression were determined using receiver-operating characteristic curves and Cox regression modeling. RESULTS: Nestin was able to distinguish cHCC-CCA from HCC with AUCs of 0.85 and 0.86 on surgical and biopsy samples, respectively. Performance was lower for the distinction of cHCC-CCA from iCCA (AUCs of 0.59 and 0.60). Nestin, however, showed a high prognostic value, allowing identification of the subset of cHCC-CCA (``Nestin High'', >30\% neoplastic cells with positive staining) associated with the worst clinical outcome (shorter disease-free and overall survival) after surgical resection and liver transplantation, as well as when assessment was performed on biopsies. CONCLUSION: We show in different clinical settings that Nestin has diagnostic value and that it is a useful biomarker to identify the subset of cHCC-CCA associated with the worst clinical outcome. Nestin immunohistochemistry may be used to refine risk stratification and improve treatment allocation for patients with this highly aggressive malignancy. LAY SUMMARY: There are different types of primary liver cancers (i.e. cancers that originate in the liver). Accurately identifying a specific subtype of primary liver cancer (and determining its associated prognosis) is important as it can have a major impact on treatment allocation. Herein, we show that a protein called Nestin could be used to refine risk stratification and improve treatment allocation for patients with combined hepatocellular carcinoma, a rare but highly aggressive subtype of primary liver cancer.

@article{Calderaro2022-ci, abstract = {BACKGROUND \& AIMS: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer (PLC) associated with a poor prognosis. Given the challenges in its identification and its clinical implications, biomarkers are critically needed. We aimed to investigate the diagnostic and prognostic value of the immunohistochemical expression of Nestin, a progenitor cell marker, in a large multicentric series of PLCs. METHODS: We collected 461 cHCC-CCA samples from 32 different clinical centers. Control cases included 368 hepatocellular carcinomas (HCCs) and 221 intrahepatic cholangiocarcinomas (iCCAs). Nestin immunohistochemistry was performed on whole tumor sections. Diagnostic and prognostic performances of Nestin expression were determined using receiver-operating characteristic curves and Cox regression modeling. RESULTS: Nestin was able to distinguish cHCC-CCA from HCC with AUCs of 0.85 and 0.86 on surgical and biopsy samples, respectively. Performance was lower for the distinction of cHCC-CCA from iCCA (AUCs of 0.59 and 0.60). Nestin, however, showed a high prognostic value, allowing identification of the subset of cHCC-CCA (``Nestin High'', >30\% neoplastic cells with positive staining) associated with the worst clinical outcome (shorter disease-free and overall survival) after surgical resection and liver transplantation, as well as when assessment was performed on biopsies. CONCLUSION: We show in different clinical settings that Nestin has diagnostic value and that it is a useful biomarker to identify the subset of cHCC-CCA associated with the worst clinical outcome. Nestin immunohistochemistry may be used to refine risk stratification and improve treatment allocation for patients with this highly aggressive malignancy. LAY SUMMARY: There are different types of primary liver cancers (i.e. cancers that originate in the liver). Accurately identifying a specific subtype of primary liver cancer (and determining its associated prognosis) is important as it can have a major impact on treatment allocation. Herein, we show that a protein called Nestin could be used to refine risk stratification and improve treatment allocation for patients with combined hepatocellular carcinoma, a rare but highly aggressive subtype of primary liver cancer.}, added-at = {2024-09-10T11:54:51.000+0200}, author = {Calderaro, Julien and Di Tommaso, Luca and Maill{\'e}, Pascale and Beaufr{\`e}re, Aur{\'e}lie and Nguyen, Cong Trung and Heij, Lara and Gnemmi, Viviane and Graham, Rondell P and Charlotte, Fr{\'e}d{\'e}ric and Chartier, Suzanne and Wendum, Dominique and Vij, Mukul and Allende, Daniela and Diaz, Alba and Fuster, Carla and Rivi{\`e}re, Benjamin and Herrero, Astrid and Augustin, J{\'e}r{\'e}my and Evert, Katja and Calvisi, Diego Francesco and Leow, Wei Qiang and Leung, Howard Ho Wai and Bednarsch, Jan and Boleslawski, Emmanuel and Rela, Mohamed and Chan, Anthony Wing-Hung and Forner, Alejandro and Reig, Maria and Pujals, Ana{\"\i}s and Favre, Loetitia and Allaire, Manon and Scatton, Olivier and Uguen, Arnaud and Tr{\'e}po, Eric and Sanchez, Lukas Otero and Chatelain, Denis and Remmelink, Myriam and Boulagnon-Rombi, Camille and Bazille, C{\'e}line and Sturm, Nathalie and Menahem, Benjamin and Frouin, Eric and Tougeron, David and Tournigand, Christophe and Kempf, Emmanuelle and Kim, Haeryoung and Ningarhari, Massih and Michalak-Provost, Sophie and Kather, Jakob Nikolas and Gouw, Annette S H and Gopal, Purva and Brustia, Raffaele and Vibert, Eric and Schulze, Kornelius and R{\"u}ther, Darius F and Weidemann, S{\"o}ren A and Rhaiem, Rami and Nault, Jean-Charles and Laurent, Alexis and Amaddeo, Giuliana and Regnault, H{\'e}l{\`e}ne and de Martin, Eleonora and Sempoux, Christine and Navale, Pooja and Shinde, Jayendra and Bacchuwar, Ketan and Westerhoff, Maria and Lo, Regina Cheuk-Lam and Sebbagh, Myl{\`e}ne and Guettier, Catherine and Lequoy, Marie and Komuta, Mina and Ziol, Marianne and Paradis, Val{\'e}rie and Shen, Jeanne and Caruso, Stefano}, biburl = {https://puma.scadsai.uni-leipzig.de/bibtex/23c525f2bebaa250e82650d16a37cef28/scadsfct}, interhash = {5e6e00b595a2ef2f496c2b1a2787d91a}, intrahash = {3c525f2bebaa250e82650d16a37cef28}, journal = {J. Hepatol.}, keywords = {cancer; carcinoma; cholangiocarcinoma; combined hepatocellular hepatocellular-cholangiocarcinoma; liver; nestin}, language = {en}, month = dec, number = 6, pages = {1586--1597}, publisher = {Elsevier BV}, timestamp = {2024-09-10T11:54:51.000+0200}, title = {Nestin as a diagnostic and prognostic marker for combined hepatocellular-cholangiocarcinoma}, volume = 77, year = 2022 }