Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Hum Pathol. 2010 Jun;41(6):859-66. doi: 10.1016/j.humpath.2009.09.018. Epub 2010 Feb 25.
Extrahepatic bile duct (EBD) carcinoma is a relatively rare neoplasm worldwide, and its prognostic outcome remains unfavorable. Therefore, it is necessary to investigate molecular biologic features of EBD carcinomas. Focal adhesion kinase (FAK) plays a pivotal role in cell adhesion, survival, migration, and signal transduction, but FAK expression in EBD carcinomas has not been evaluated. We measured FAK expression in 76 EBD carcinomas using immunohistochemistry and evaluated its correlation with tumor progression, clinicopathologic factors, and patient outcome. FAK was expressed specifically in the cytoplasm of all normal biliary epithelia (100%). Most dysplastic epithelia also showed positive FAK expression except for 2 cases (92%), whereas EBD carcinomas showed positive FAK expression in 53 (77%) of 76 cases (P < .001, versus normal epithelia). FAK expression tended to be gradually reduced along as dysplasia progressed to carcinoma. Although FAK expression had no association with clinicopathologic factors, the positive FAK expression group showed significantly better survival than the negative FAK expression group (P < .05). However, FAK expression was not an independent prognostic factor by multivariate analysis. In conclusion, FAK expression was significantly lower in EBD carcinomas than in normal biliary epithelia and decreased expression of FAK seemed to be indicative of a poor prognosis, suggesting that FAK might play an inhibitory role for tumor progression in EBD carcinomas. It is important to notice the role of FAK in tumor progression when treatments targeting FAK are performed.
肝外胆管（EBD）癌在全球范围内是一种相对罕见的肿瘤，其预后结果仍然不佳。因此，有必要研究 EBD 癌的分子生物学特征。粘着斑激酶（FAK）在细胞黏附、存活、迁移和信号转导中起关键作用，但尚未评估 FAK 在 EBD 癌中的表达。我们使用免疫组织化学法测量了 76 例 EBD 癌中的 FAK 表达，并评估了其与肿瘤进展、临床病理因素和患者预后的相关性。FAK 在所有正常胆管上皮中均特异性表达于细胞质（100%）。除 2 例（92%）外，大多数发育不良上皮也显示出阳性 FAK 表达，而 EBD 癌中有 53 例（77%）（P<0.001，与正常上皮相比）显示阳性 FAK 表达。FAK 表达随着发育不良进展为癌而逐渐降低。尽管 FAK 表达与临床病理因素无关，但阳性 FAK 表达组的生存情况明显优于阴性 FAK 表达组（P<0.05）。然而，FAK 表达在多因素分析中不是独立的预后因素。总之，与正常胆管上皮相比，EBD 癌中的 FAK 表达明显降低，FAK 表达降低似乎预示着预后不良，提示 FAK 可能在 EBD 癌的肿瘤进展中起抑制作用。在进行针对 FAK 的治疗时，注意 FAK 在肿瘤进展中的作用非常重要。
