Ho Joanna-W, Poon Ronnie-T, Sun Chris-K, Xue Wei-Cheng, Fan Sheung-Tat
Centre for the Study of Liver Disease, and Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China.
World J Gastroenterol. 2005 Jan 14;11(2):176-81. doi: 10.3748/wjg.v11.i2.176.
The expression pattern of endoglin (CD105) in hepatocellular carcinoma (HCC) has not been reported so far. We hypothesized that CD105 could differentially highlight a subset of microvessels in HCC, and intratumoral microvessel density (IMVD) by CD105 immunostaining (IMVD-CD105) could provide better prognostic information than IMVD by CD34 immunostaining (IMVD-CD34).
Paraffin blocks of tumor and adjacent non-tumorous liver tissues from 86 patients who underwent curative resection of HCC were used for this study. Serial sections were stained for CD105 and CD34, respectively, to highlight the microvessels. IMVD was counted according to a standard protocol.
In the HCC tissues, CD105 was either negatively or positively stained only in a subset of microvessels. In contrast, CD34 showed positive and more extensive microvessel staining in all cases examined. However, in the adjacent non-tumorous liver sections, CD105 showed a diffuse pattern of microvessel staining in 20 of 86 cases, while CD34 showed negative or only focal staining of the sinusoids around portal area. Correlation with clinicopathological data demonstrated that lower scores of IMVD-CD105 were found in larger sized tumors (mean 41.4/0.74 mm2 (>5 cm tumor) vs 65.9/0.74 mm2 (< or =5 cm tumor), P = 0.043) and more aggressive tumors, as indicated by venous infiltration (36.8/0.74 mm2 (present) vs 64.2/0.74 mm2 (absent), P = 0.020), microsatellite nodules (35.1/0.74 mm2 (present) vs 65.9/0.74 mm2 (absent), P = 0.012), and advanced TNM tumor stage (38.8/0.74 mm2 (stage 3 or 4) vs 68.3/0.74 mm2 (stage 1 or 2), P = 0.014). No prognostic significance was observed when median values were used as cut-off points using either IMVD-CD105 or IMVD-CD34. However, the presence of the diffuse pattern of CD105 expression in the adjacent non-tumorous liver tissues predicted a poorer disease-free survival (median 8.6 vs 21.5 mo, P = 0.026).
Our data demonstrate that a lower IMVD-CD105 is associated with larger and more aggressive tumors. In this study, IMVD-CD105 did not provide significant prognostic information. However, active angiogenesis as highlighted by diffuse CD105 staining of the microvessels in the adjacent non-tumorous liver tissues is predictive of early recurrence.
目前尚未见关于内皮糖蛋白（CD105）在肝细胞癌（HCC）中表达模式的报道。我们推测CD105可特异性地突显HCC中的一部分微血管，并且通过CD105免疫染色测定的瘤内微血管密度（IMVD-CD105）比通过CD34免疫染色测定的IMVD（IMVD-CD34）能提供更好的预后信息。
本研究采用86例行HCC根治性切除术患者的肿瘤及癌旁非肿瘤肝组织石蜡块。连续切片分别进行CD105和CD34染色以突显微血管。按照标准方案计数IMVD。
在HCC组织中，CD105仅在一部分微血管中呈阴性或阳性染色。相比之下，CD34在所有检测病例中均显示阳性且微血管染色范围更广。然而，在癌旁非肿瘤肝组织切片中，86例中有20例CD105显示微血管弥漫性染色，而CD34显示门静脉周围肝血窦呈阴性或仅局灶性染色。与临床病理数据的相关性分析表明，在肿瘤体积较大的患者中IMVD-CD105得分较低（平均41.4/0.74mm²（肿瘤＞5cm）对65.9/0.74mm²（肿瘤≤5cm），P = 0.043），在侵袭性更强的肿瘤中也是如此，如静脉浸润（36.8/0.74mm²（存在）对64.2/0.74mm²（不存在），P = 0.020）、微卫星结节（35.1/0.74mm²（存在）对65.9/0.74mm²（不存在），P = 0.012）以及TNM肿瘤分期较晚（38.8/0.74mm²（3期或4期）对68.3/0.74mm²（1期或2期），P = 0.014）。以IMVD-CD105或IMVD-CD34的中位数作为截断点时，未观察到预后意义。然而，癌旁非肿瘤肝组织中CD105表达呈弥漫性模式提示无病生存期较差（中位数8.6个月对21.5个月，P = 0.026）。
我们的数据表明，较低的IMVD-CD105与更大且侵袭性更强 的肿瘤相关。在本研究中，IMVD-CD105未提供显著的预后信息。然而，癌旁非肿瘤肝组织中微血管CD105弥漫性染色突显的活跃血管生成可预测早期复发。
