Research Papers:

Mutational profile of skin lesions in hepatocellular carcinoma patients under tyrosine kinase inhibition: a repercussion of a wide-spectrum activity

Leonardo G. da Fonseca, Carla Fuster-Anglada, Cristina Carrera, Cristina Millán, Esther Samper, Victor Sapena, Álvaro Díaz-González, Marco Sanduzzi-Zamparelli, Cassia Leal, Alejandro Forner, Jordi Bruix, Maria Reig, Loreto Boix _ and Alba Díaz _

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Oncotarget. 2021; 12:440-449. https://doi.org/10.18632/oncotarget.27891

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Leonardo G. da Fonseca1,*, Carla Fuster-Anglada2,*, Cristina Carrera3, Cristina Millán1, Esther Samper1, Victor Sapena1, Álvaro Díaz-González1, Marco Sanduzzi-Zamparelli1, Cassia Leal1, Alejandro Forner1, Jordi Bruix1, Maria Reig1, Loreto Boix1,# and Alba Díaz2,#

1 Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clínic de Barcelona, IDIBAPS, Universitat de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain

2 Barcelona Clinic Liver Cancer (BCLC) Group, Department of Pathology, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain

3 Melanoma Unit, Dermatology Department, Hospital Clínic de Barcelona, Universitat de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain

* Authors collaborated equally as first author

# Authors collaborated equally as senior author

Correspondence to:

Loreto Boix,email: [email protected]
Alba Díaz,email: [email protected]

Keywords: hepatocellular carcinoma; tyrosine kinase inhibitors; treatment adverse events; skin lesions; molecular profiling

Received: January 05, 2021     Accepted: February 01, 2021     Published: March 02, 2021

Copyright: © 2021 da Fonseca et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Background/Aim: Dermatological adverse events (DAE) in hepatocellular carcinoma (HCC) patients treated with sorafenib predicts better outcome. Some turn into skin lesions (SL) requiring pathology examination. We describe incidence, characteristics and molecular profile of SL in HCC patients treated with sorafenib.

Materials and Methods: SL were prospectively collected in 311 HCC patients who started sorafenib. SL from sorafenib cohort were compared to those from a control patient group selected to match SL type and demographics. HRAS, KRAS and BRAF mutations were analyzed by CAST-PCR, mutated p53 and MAPK pathway activation by immunohistochemistry and immune infiltration by hematoxylin-eosin staining.

Results: Eighty-eight out of 311 patients developed DAE and 7.4% SL required histological assessment. Most frequent lesions were keratoacanthomas (n = 4), squamous-cell carcinomas (SCC)(n = 5), basal-cell carcinomas (BCC)(n = 3) and seborrheic keratosis (n = 5). HRAS and KRAS mutations were detected in 4 SL, while no mutations showed in control SL. Nuclear pERK immunostaining was identified in 33.3% of cases versus 5.3% of controls. Most SL (90%) from patients with DAE were proliferative with intense immune infiltration (73%).

Conclusions: The onset of SL and their molecular profile did not impact negatively on patient’s prognosis, but intense proliferation of SL may reflect compensatory activation of MAPK pathway and warrants their close monitoring.

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