粗梁实体型肝细胞癌的强侵袭性临床特征与不良预后分析

Analysis of strong invasive clinical features and poor prognosis in macrotrabecular-massive hepatocellular carcinoma

目的分析肝细胞癌(HCC)组织学分型,特别是粗梁实体(MTM)型与肿瘤侵袭性及预后的相关性。方法回顾性分析2015至2018年符合纳入标准连续246例HCC患者的临床和随访资料,依据组织学分型分为细梁/假腺管型、粗梁/团片型、MTM型,分析各型与相关临床病理特征关系,Kaplan-Meier法绘制无瘤生存率(DFS)和总生存率(OS)曲线并行Log-rank检验,COX单因素及多因素回归分析包括组织学分型在内的临床特征与DFS和OS关系。结果细梁/假腺管型、粗梁/团片型、MTM型比例分别为44.7%(110例)、32.9%(81例)和22.4%(55例)。结果显示,MTM型HCC中提示高侵袭性的临床病理特征甲胎蛋白(AFP)≥400 ng/ml、肿瘤直径≥8 cm、无肿瘤包膜、分化差、微血管侵犯(MVI)阳性比例显著高于其他2种类型,差异均有统计学意义(P值均<0.05)。MTM型HCC TNM Ⅲ~IV期和中国肝癌分期(CNLC)Ⅱ~Ⅱ期患者的比例显著也高于其他2种类型,差异均有统计学意义(P值均<0.05),且MTM亚型行经导管动脉化疗栓塞术比例也较高(P<0.05)。MTM型HCC的1、3、5年DFS和OS显著低于细梁/假腺管型HCC的1、3、5年DFS和OS,差异均有统计学意义(P值均<0.05)。单因素分析提示高侵袭性的临床病理特征甲胎蛋白(AFP)≥400 ng/ml、肿瘤直径≥8 cm、无肿瘤包膜、分化差、微血管侵犯阳性、肿瘤分期和MTM分型均是影响DFS和OS的危险因素(P值均<0.05)。多因素COX分析显示MTM组织学分型、AFP≥400 ng/ml、肿瘤无包膜、卫星灶、CNLC Ⅱ~Ⅲ期及TNM Ⅲ~Ⅳ期是DFS的独立危险因素(P值均<0.05);而AFP≥400 ng/ml、肿瘤无包膜和CNLC Ⅱ~Ⅲ期是OS的独立危险因素(P值均<0.05)。结论组织学分型与HCC肿瘤侵袭性和预后高度相关,细梁/假腺管型恶性程度较低,预后较好,而MTM型则表现出强侵袭性特征,预后不良。

Objective To analyze the correlation between the histological classification of hepatocellular carcinoma(HCC),especially macrotrabecular-massive(MTM),tumor invasiveness,and prognosis.Methods The clinical and follow-up data of 246 consecutive HCC cases who met the inclusion criteria from 2015 to 2018 were retrospectively analyzed.They were divided into trabecular/pseudoglandular,trabecular/patchy,and MTM types according to the histological classification.The relationship between each type and related clinicopathological features was analyzed.The Kaplan-Meier method was used to plot tumor-free survival(DFS)and overall survival(OS)curves.Log rank tests,COX univariate,and multivariate regression analyses were conducted to analyze the relationship between clinical features,including histological classification,DFS,and OS.Results Trabecular/pseudoglandular,trabecular/nodular,and MTM type proportions were 44.7%(110 cases),32.9%(81 cases),and 22.4%(55 cases),respectively.The results of the clinicopathological features showed that MTM-type HCC was significantly more invasive than the other two types,with alpha-fetoprotein(AFP)≥400 ng/ml,tumor diameter≥8 cm,no tumor capsule,poor differentiation,and MVI positivity proportions,and the differences were statistically significant(P<0.05).The proportion of MTM-type HCC patients with American Joint Committee on Cancer TNM Stage Ⅲ to IV and Chinese Liver Cancer Staging(CNLC)Ⅱ to Ⅱ was significantly higher than that of the first two types,and the differences were statistically significant(P<0.05).In addition,the proportion of MTM subtypes undergoing transcatheter arterial chemoembolization was also raised(P<0.05).The DFS and OS were significantly lower for MTM-type HCC compared to trabecular/pseudoductal-type HCC at 1-,3-,and 5-years,and the differences were statistically significant(P<0.05).Univariate analysis indicated that strongly invasive clinical pathological features such as alpha fetoprotein(AFP)≥400 ng/ml,tumor diameter≥8 cm,no tumor capsule,poor differentiation,positive microvascular invasion,tumor stage,and MTM staging were all risk factors affecting DFS and OS(P<0.05).Multivariate COX analysis showed that MTM histological staging,AFP≥400 ng/ml,tumor non-encapsulation,satellite nodules,CNLC stages Ⅱ~Ⅲ,and TNM stages Ⅲ~Ⅳ were independent risk factors for DFS(P<0.05),while AFP≥400 ng/ml,tumor non-encapsulation,and CNLC stage Ⅱ~Ⅲ were independent risk factors for OS(P<0.05).Conclusion Histological classification is highly correlated with tumor invasiveness and HCC prognosis.Trabecular/pseudoglandular types have lower malignancy and a better prognosis,while MTM types exhibit strong invasive features and a poor prognosis.