Romani Antonello A, Soliani Paolo, Desenzani Silvia, Borghetti Angelo F, Crafa Pellegrino
Dipartimento di Medicina Sperimentale--Sezione di Patologia Molecolare ed Immunologia, Università degli Studi di Parma, 43100 Parma, Italy.
BMC Cancer. 2006 Oct 26;6:255. doi: 10.1186/1471-2407-6-255.
Maspin, a member of the serpin family, is a suppressor of tumor growth, an inhibitor of angiogenesis and an inducer of apoptosis. Maspin induces apoptosis by increasing Bax, a member of the Bcl-2 family of apoptosis-regulating proteins. In this exploratory study, we investigated the associated expression of Maspin and Bax proteins as a potential prognostic factor in intrahepatic cholangiocarcinoma (IHCCA).
Twenty-two paraffin-embedded samples were analyzed by immunohistochemical methods using Maspin, Bax and CD34 antibodies. Maspin was scored semiquantitatively (HSCORE). Apoptosis was assessed using an antibody against cleaved caspase-3.
The strong relationship observed between the expression of Maspin and Bax, indicates that Bax is likely to be the key effector of Maspin-mediated induction of apoptosis as indicated by the activation of cleaved caspase-3. We categorized Maspin HSCORE by calculating the optimal cutpoint. A Maspin HSCORE above the cutpoint was inversely related with tumor dimension, depth of tumor and vascular invasion. Uni/multivariate analysis suggests that a Maspin HSCORE below the cutpoint significantly worsens the patients' prognosis. Tumors with Maspin HSCORE below the cutpoint had a shorter survival (11+/-5 months) than did patients with Maspin HSCORE above the cutpoint (27+/-4 months), whereas Kaplan-Meier analysis and logrank test showed no significant difference in overall survival between the patients.
The associated expression of Maspin and Bax might delay tumor progression in IHCCA. Maspin above the cutpoint might counteract tumor development by increasing cell apoptosis, and by decreasing tumor mass and cell invasion. The combined expression of Maspin and Bax appears to influence the susceptibility of tumor cholangiocytes to apoptosis and thus may be involved in delaying IHCCA progression.
Maspin是丝氨酸蛋白酶抑制剂家族的成员，是肿瘤生长的抑制因子、血管生成的抑制剂和细胞凋亡的诱导剂。Maspin通过增加Bax（一种凋亡调节蛋白Bcl-2家族的成员）来诱导细胞凋亡。在这项探索性研究中，我们研究了Maspin和Bax蛋白的联合表达作为肝内胆管癌（IHCCA）潜在预后因素的情况。
使用Maspin、Bax和CD34抗体，通过免疫组织化学方法对22个石蜡包埋样本进行分析。Maspin进行半定量评分（HSCORE）。使用抗裂解的半胱天冬酶-3抗体评估细胞凋亡。
观察到Maspin和Bax表达之间存在密切关系，这表明如裂解的半胱天冬酶-3的激活所示，Bax可能是Maspin介导的细胞凋亡诱导的关键效应因子。我们通过计算最佳切点对Maspin HSCORE进行分类。高于切点的Maspin HSCORE与肿瘤大小、肿瘤深度和血管侵犯呈负相关。单因素/多因素分析表明，低于切点的Maspin HSCORE显著恶化患者的预后。Maspin HSCORE低于切点的肿瘤患者生存期（11±5个月）短于Maspin HSCORE高于切点的患者（27±4个月），而Kaplan-Meier分析和对数秩检验显示患者总体生存期无显著差异。
Maspin和Bax的联合表达可能会延缓IHCCA的肿瘤进展。高于切点的Maspin可能通过增加细胞凋亡、减少肿瘤体积和细胞侵袭来对抗肿瘤发展。Maspin和Bax的联合表达似乎会影响肿瘤胆管细胞对细胞凋亡的易感性，因此可能参与延缓IHCCA的进展。
