Ohashi K, Nakajima Y, Kanehiro H, Tsutsumi M, Taki J, Aomatsu Y, Yoshimura A, Ko S, Kin T, Yagura K
First Department of Surgery, Nara Medical University, Japan.
Gastroenterology. 1995 Nov;109(5):1612-7. doi: 10.1016/0016-5085(95)90650-9.
BACKGROUND & AIMS: We previously reported that intrahepatic cholangiocarcinomas (ICCs) can be divided into three categories according to their gross appearance with possible links to biological behavior. Ki-ras and p53 gene alterations are thought to be involved in early and late phases of carcinogenesis, respectively. This study was performed to investigate the relationship between the gross appearance and genetic alterations of ICC.
We examined 21 patients with ICC. Ki-ras point mutations were assessed by polymerase chain reaction/single-strand conformation polymorphism methods followed by direct DNA sequencing. Expressions of p53 protein were immunohistochemically assessed.
Ki-ras point mutations were found in 10 patients (48%), and expressions of p53 protein were detected in 4 (19%). Applying the gross classification that we previously proposed, Ki-ras mutations were prominent in the periductal extension type (4 of 6; 67%) and the spicula-forming type (6 of 10; 60%). On the other hand, none of the five mass-forming-type tumors harbored Ki-ras mutations. Expressions of p53 protein did not show any clear association with gross appearance.
Ki-ras gene alterations may be involved in the cholangiocarcinogenesis of periductal extension and spicula-forming but not mass-forming types, suggesting that the underlying processes of development are different.
我们之前报道过，肝内胆管癌（ICC）可根据大体外观分为三类，这可能与生物学行为相关。Ki-ras和p53基因改变分别被认为参与了致癌作用的早期和晚期阶段。本研究旨在探讨ICC大体外观与基因改变之间的关系。
我们检查了21例ICC患者。通过聚合酶链反应/单链构象多态性方法并随后进行直接DNA测序来评估Ki-ras点突变。通过免疫组织化学评估p53蛋白的表达。
在10例患者（48%）中发现了Ki-ras点突变，在4例（19%）中检测到了p53蛋白的表达。应用我们之前提出的大体分类，Ki-ras突变在导管周围浸润型（6例中的4例；67%）和毛刺形成型（10例中的6例；60%）中较为突出。另一方面，5例肿块形成型肿瘤均未发生Ki-ras突变。p53蛋白的表达与大体外观未显示出任何明确的关联。
Ki-ras基因改变可能参与了导管周围浸润型和毛刺形成型而非肿块形成型的胆管癌发生过程，提示其潜在的发展过程有所不同。
