Kirimlioglu H, Dvorchick I, Ruppert K, Finkelstein S, Marsh J W, Iwatsuki S, Bonham A, Carr B, Nalesnik M, Michalopoulos G, Starzl T, Fung J, Demetris A
Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA.
Hepatology. 2001 Sep;34(3):502-10. doi: 10.1053/jhep.2001.26633.
The gross and histopathologic characteristics of 212 nonfibrolamellar hepatocellular carcinomas (HCCs) discovered in native livers removed at the time of liver transplantation were correlated with features of invasive growth and tumor-free survival. The results show that most HCCs begin as small well-differentiated tumors that have an increased proliferation rate and induce neovascularization, compared with the surrounding liver. But at this stage, they maintain a near-normal apoptosis/mitosis ratio and uncommonly show vascular invasion. As tumors enlarge, foci of dedifferentiation appear within the neoplastic nodules, which have a higher proliferation rate and show more pleomorphism than surrounding better-differentiated areas. Vascular invasion, which is the strongest predictor of disease recurrence, correlates significantly with tumor number and size, tumor giant cells and necrosis, the predominant and worst degree of differentiation, and the apoptosis/mitosis ratio. In the absence of macroscopic or large vessel invasion, largest tumor size (P <.006), apoptosis/mitosis ratio (P <.03), and number of tumors (P <.04) were independent predictors of tumor-free survival and none of 24 patients with tumors having an apoptosis/mitosis ratio greater than 7.2 had recurrence. A minority of HCCs (<15%) quickly develop aggressive features (moderate or poor differentiation, low apoptosis/mitosis ratio, and vascular invasion) while still small, similar to flat carcinomas of the bladder and colon. In conclusion, hepatic carcinogenesis in humans is a multistep and multifocal process. As in experimental animal studies, aggressive biologic behavior (vascular invasion and recurrence) correlates significantly with profound alterations in the apoptosis/mitosis ratio and with architectural and cytologic alterations that suggest a progressive accumulation of multiple genetic abnormalities.
对212例在肝移植时切除的原位肝脏中发现的非纤维板层型肝细胞癌（HCC）的大体和组织病理学特征，与侵袭性生长特征及无瘤生存期进行了相关性分析。结果显示，大多数HCC起初为小的高分化肿瘤，与周围肝脏相比，其增殖率增加并诱导新生血管形成。但在此阶段，它们保持接近正常的凋亡/有丝分裂比率，且很少出现血管侵犯。随着肿瘤增大，肿瘤结节内出现去分化灶，其增殖率更高，与周围高分化区域相比表现出更多的多形性。血管侵犯是疾病复发的最强预测指标，与肿瘤数量和大小、肿瘤巨细胞和坏死、主要及最差分化程度以及凋亡/有丝分裂比率显著相关。在无宏观或大血管侵犯的情况下，最大肿瘤大小（P <.006）、凋亡/有丝分裂比率（P <.03）和肿瘤数量（P <.04）是无瘤生存期的独立预测指标，24例凋亡/有丝分裂比率大于7.2的肿瘤患者均无复发。少数HCC（<15%）在仍较小时就迅速出现侵袭性特征（中度或低分化、低凋亡/有丝分裂比率和血管侵犯），类似于膀胱和结肠的扁平癌。总之，人类肝癌发生是一个多步骤、多灶性过程。如同在实验动物研究中一样，侵袭性生物学行为（血管侵犯和复发）与凋亡/有丝分裂比率的深刻改变以及提示多种基因异常逐渐积累的结构和细胞学改变显著相关。
