Saurin J C, Joly-Pharaboz M O, Pernas P, Henry L, Ponchon T, Madjar J J
Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Lyon, France.
Gut. 2000 Sep;47(3):357-61. doi: 10.1136/gut.47.3.357.
The present study was undertaken to determine if detection of Ki-ras gene point mutations in bile specimens could differentiate between benign and malignant biliary strictures.
Bile specimens were obtained from 117 patients exhibiting a stricture of the main bile duct, the nature of which was assessed by cholangiography, histology, and follow up.
DNA from frozen bile specimens was extracted, amplified, and tested for codon 12 point mutations of Ki-ras gene using sequence specific oligonucleotide hybridisation and mutant allele specific amplification.
DNA amplification was successful in 110/117 bile specimens (94%). Detection of Ki-ras gene mutations in bile specimens was positive in 24.4% (22/90) of patients with malignant strictures, in 31.4% (22/70) when only primary malignant tumours were considered, and in 4% (1/25) of patients with benign strictures. Of the 49 patients with histological specimens obtained before surgery, the sensitivity of histology, Ki-ras mutation analysis, and combined methods was 59.2%, 28.6%, and 73.5% respectively.
Our study showed that Ki-ras mutations may be detected in about one third of bile specimens from patients with primary tumours invading the main bile duct. Detection of such mutations appears to be specific and may help to differentiate between benign and malignant biliary strictures.
本研究旨在确定检测胆汁标本中Ki-ras基因点突变能否区分良性和恶性胆管狭窄。
从117例表现为肝总管狭窄的患者获取胆汁标本，通过胆管造影、组织学检查及随访评估其狭窄的性质。
提取、扩增冷冻胆汁标本中的DNA，采用序列特异性寡核苷酸杂交和突变等位基因特异性扩增技术检测Ki-ras基因第12密码子点突变。
117份胆汁标本中有110份（94%）成功进行了DNA扩增。胆汁标本中Ki-ras基因突变检测在恶性狭窄患者中阳性率为24.4%（22/90），仅考虑原发性恶性肿瘤时为31.4%（22/70），良性狭窄患者中为4%（1/25）。在术前获取组织学标本的49例患者中，组织学检查、Ki-ras突变分析及联合方法的敏感性分别为59.2%、28.6%和73.5%。
我们的研究表明，在原发性肿瘤侵犯肝总管的患者中，约三分之一的胆汁标本可检测到Ki-ras突变。此类突变的检测似乎具有特异性，可能有助于区分良性和恶性胆管狭窄。
