Sciarra Amedeo, Pintea Bogdan, Nahm Ji Hae, Donadon Matteo, Morenghi Emanuela, Maggioni Marco, Blanc Jean Frederic, Torzilli Guido, Yeh Matthew, Bioulac-Sage Paulette, Park Young Nyun, Roncalli Massimo, Di Tommaso Luca
University of Milan School of Medicine, Milan, Italy.
University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania.
Dig Liver Dis. 2017 Apr;49(4):434-439. doi: 10.1016/j.dld.2016.12.002. Epub 2016 Dec 16.
Although hepatic resection is a potentially curative treatment for hepatocellular carcinoma (HCC), post-operative prognosis remains unsatisfactory due to the high incidence of recurrence. Several clinicopathological markers have been associated with HCC recurrence, but none has been validated. Extratumoral expression of cytochrome P4501A2 (CYP1A2) was recently proposed as predictor of HCC recurrence.
To validate extratumoral CYP1A2 as predictor of HCC recurrence and to determine its applicability to pretreatment liver biopsy.
Surgically resected HCC (n.180) with clinicopathological data and follow up were retrospectively studied (HCV n.54; HBV n.91; NAFLD/NASH n.35). CYP1A2 expression was evaluated using an immunohistochemical assay and semiquantitative analysis.
Etiology-stratified analysis showed that low CYP1A2 expression was independently associated with recurrence-free survival in HCV patients (HR 2.814, 95% CI 1.300-6.093, p=0.009); this association was lost in the whole cohort. Pretreatment liver biopsy and paired surgical specimens showed concordant CYP1A2 expression in the vast majority of cases (87%), with NPV of 100%, PPV of 81.25%, and a Cohen kappa of 0.72 (substantial agreement).
We validated the extratumoral expression of CYP1A2 as a biomarker of HCC recurrence in HCV patients. CYP1A2 analysis in pretreatment liver biopsy can be of help to stratify HCC patients for personalized treatment.
尽管肝切除术是肝细胞癌(HCC)潜在的治愈性治疗方法,但由于复发率高,术后预后仍不尽人意。几种临床病理标志物与HCC复发相关,但均未得到验证。细胞色素P4501A2(CYP1A2)的肿瘤外表达最近被提出作为HCC复发的预测指标。
验证肿瘤外CYP1A2作为HCC复发的预测指标,并确定其在术前肝活检中的适用性。
回顾性研究180例手术切除的HCC患者,记录其临床病理数据并进行随访(丙型肝炎病毒感染患者54例;乙型肝炎病毒感染患者91例;非酒精性脂肪性肝病/非酒精性脂肪性肝炎患者35例)。采用免疫组织化学分析和半定量分析评估CYP1A2的表达。
病因分层分析显示,低CYP1A2表达与丙型肝炎病毒感染患者的无复发生存独立相关(风险比2.814,95%可信区间1.300-6.093,p=0.009);在整个队列中这种相关性消失。术前肝活检和配对手术标本在绝大多数病例(87%)中显示CYP1A2表达一致,阴性预测值为100%,阳性预测值为81.25%,科恩kappa系数为0.72(高度一致)。
我们验证了肿瘤外CYP1A2表达作为丙型肝炎病毒感染患者HCC复发的生物标志物。术前肝活检中的CYP1A2分析有助于对HCC患者进行分层以实现个性化治疗。