da Fonseca Leonardo G, Fuster-Anglada Carla, Carrera Cristina, Millán Cristina, Samper Esther, Sapena Victor, Díaz-González Álvaro, Sanduzzi-Zamparelli Marco, Leal Cassia, Forner Alejandro, Bruix Jordi, Reig Maria, Boix Loreto, Díaz Alba
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.
Authors collaborated equally as first author.
Oncotarget. 2021 Mar 2;12(5):440-449. doi: 10.18632/oncotarget.27891.
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.
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. , and mutations were analyzed by CAST-PCR, mutated p53 and MAPK pathway activation by immunohistochemistry and immune infiltration by hematoxylin-eosin staining.
Eighty-eight out of 311 patients developed DAE and 7.4% SL required histological assessment. Most frequent lesions were keratoacanthomas ( = 4), squamous-cell carcinomas (SCC)( = 5), basal-cell carcinomas (BCC)( = 3) and seborrheic keratosis ( = 5). and 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%).
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.
背景/目的：接受索拉非尼治疗的肝细胞癌（HCC）患者发生皮肤不良事件（DAE）预示着更好的预后。有些会演变成需要病理检查的皮肤病变（SL）。我们描述了接受索拉非尼治疗的HCC患者中SL的发生率、特征和分子谱。
前瞻性收集311例开始使用索拉非尼治疗的HCC患者的SL。将索拉非尼队列中的SL与根据SL类型和人口统计学选择的对照患者组的SL进行比较。通过CAST-PCR分析、 、 和 突变，通过免疫组织化学分析突变型p53和MAPK途径激活情况，并通过苏木精-伊红染色分析免疫浸润情况。
311例患者中有88例发生DAE，7.4%的SL需要组织学评估。最常见的病变是角化棘皮瘤（ = 4）、鳞状细胞癌（SCC）（ = 5）、基底细胞癌（BCC）（ = 3）和脂溢性角化病（ = 5）。在4例SL中检测到 和 突变，而对照SL中未显示突变。33.3%的病例中检测到核pERK免疫染色，而对照中为5.3%。来自发生DAE患者的大多数SL（90%）呈增殖性，伴有强烈的免疫浸润（73%）。
SL的发生及其分子谱对患者预后没有负面影响，但SL的强烈增殖可能反映MAPK途径的代偿性激活，需要对其进行密切监测。
