Diniz Paulo H C, Silva Serena D C, Vidigal Paula V T, Xavier Marcelo A P, Lima Cristiano X, Faria Luciana C, Ferrari Teresa C A
Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Departamento de Anatomia Patológica e Medicina Legal, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
J Oncol. 2020 Oct 29;2020:4609360. doi: 10.1155/2020/4609360. eCollection 2020.
Chronic liver disease (CLD) of different etiologies leads to hepatocellular carcinoma (HCC) by multiple mechanisms that may be translated into clinicopathological differences. We evaluated the tissue expression of the MAPK and PI3K/Akt/mTOR pathway proteins and their association with long-term outcome and other parameters, according to the etiology of the CLD, in HCC patients.
Clinicopathological data from 80 patients who underwent orthotopic liver transplantation for HCC treatment in a Brazilian referral center were compared according to CLD etiology. Event (tumor recurrence or death from any cause) occurrence and event-free survival (EFS) were analyzed. Pathway protein expression was assessed by immunohistochemistry (IHQ) in both tumor and underlying cirrhosis and by RT-PCR in tumor tissue.
Strong expression (SE) of KRAS was more frequent in tumors arising from viral (26.8%) than the nonviral group of liver disease (7.7%, =0.024) and also than cirrhotic parenchyma (0%, =0.004). SE of PI3K was more frequent in tumor than in cirrhosis (=0.048, < 0.01), without differences in its tumor expression among etiologic groups (=0.111). mRNA of ERK, PI3K, and BRAF was expressed in the tumor, without differences between CLD etiologies, and there was no association with IHQ findings. Older age and microvascular invasion (MIV) were the only parameters independently associated with the event. MIV was also associated with shorter EFS.
Hepatitis B and C virus can lead to HCC by different mechanisms compared with nonviral hepatopathy. KRAS and PI3K may have a role in carcinogenesis. The prognostic and therapeutic implications need to be investigated.
不同病因的慢性肝病（CLD）通过多种机制导致肝细胞癌（HCC），这些机制可能转化为临床病理差异。我们根据CLD的病因，评估了HCC患者中MAPK和PI3K/Akt/mTOR信号通路蛋白的组织表达及其与长期预后和其他参数的关联。
比较了巴西一家转诊中心80例因HCC接受原位肝移植患者的临床病理数据，并根据CLD病因进行分组。分析了事件（肿瘤复发或任何原因导致的死亡）的发生情况和无事件生存期（EFS）。通过免疫组织化学（IHQ）评估肿瘤和潜在肝硬化组织中信号通路蛋白的表达，并通过RT-PCR检测肿瘤组织中的表达。
KRAS的强表达（SE）在病毒性肝病引起的肿瘤中更为常见（26.8%），高于非病毒性肝病组（7.7%，P=0.024），也高于肝硬化实质组织（0%，P=0.004）。PI3K的SE在肿瘤中比在肝硬化中更常见（P=0.048，P<0.01），在不同病因组的肿瘤表达中无差异（P=0.111）。肿瘤组织中表达ERK、PI3K和BRAF的mRNA，不同CLD病因之间无差异，且与IHQ结果无关联。年龄较大和微血管侵犯（MIV）是与事件独立相关的唯一参数。MIV也与较短的EFS相关。
与非病毒性肝病相比，乙型和丙型肝炎病毒可通过不同机制导致HCC。KRAS和PI3K可能在致癌过程中起作用。其预后和治疗意义有待进一步研究。
