Genetic study on mode of tumor spread from colorectal metastasis in the liver -standardization of surgical procedure

为了阐明结直肠癌肝转移手术切除的最合理方法，我们进行了一项遗传学和组织学研究。采用基因诊断方法，对肝实质内和Glisson‘s区肿瘤进行了研究。我们还研究了K-ras和p-53基因突变对肝切除术后患者生存的影响。从1996年到2002年，58例结直肠癌肝转移患者接受了62例肝切除术。取自肿瘤、周围肝实质和肿瘤附近的Glisson椎弓根的组织样本用突变等位基因特异性扩增方法检测K-ras和p-53突变。这个队列被跟踪到2004年1月，并分析了患者的存活率。在62例肝转移癌标本中，39例K-ras和/或p53基因突变阳性。2.0%(4/199)的受检者在结直肠癌转移灶周围肝实质内存在微转移，转移灶位于肿瘤边缘4 mm以内。经Glisson‘s蒂的微转移更常见(14.3%：3/21)，但也局限在距肿瘤边缘较短的范围内(小于或等于5 mm)。两种基因均无突变的患者三年生存率为94%，有WISTER基因突变的患者三年生存率为67%(P=0.177)。K-ras基因突变患者的三年生存率明显低于无突变患者(p=0.045)，肝肿瘤周围微转移并不常见，多局限于肿瘤边缘。手术切缘2毫米似乎是临床可接受的最低要求，与切缘相关的复发风险约为5%。转移性病变中的K-ras突变与肝切除术后患者预后不良有关。

To clarify most reasonable procedures for the surgical resection of colorectal liver metastases, we have conducted a genetic and histological study. Using a genetic diagnosis, tumor supread inside the hepatic parenchyma and Glisson's were investigated. Impact of K-ras and p-53 mutations on patient survival after liver resection was also studied. From 1996 through 2002,58 patients underwent 62 liver resections for hepatic metastasis from colorectal cancer. Tissue samples taken from the tumor, the surrounding liver parenchyma, and Glisson's pedicle near the tumor were tested for K-ras and p-53 mutations using the mutant allele-specific amplification method. This cohort was followed up until January 2004, and patient survival was analyzed. Of the 62 sets of samples from liver metastases, 39 were positive for K-ras and/or p53 gene mutations. Micrometastases in the liver parenchyma surrounding colorectal metastases were present in 2.0% (4/199) of tested samples and were located within 4 mm from the tumor border.Micrometastases via Glisson's pedicle were more common (14.3%:3/21), but they were also confined to a short range from the tumor edge (【less than or equal】 5mm). Three-year survival rate of patients without mutations of either gene was 94% while that of patients with mutation of wither gene was 67% (p=0.177 logrank). Three-year survival rate of patients with K-ras mutation had significantly poor prognosis comapring to that of patients without mutation (p=0.045).Micrometastases around the liver tumors are not common and most are confined to the immediate vicinity of the tumor border. Surgical margin of 2 mm appears to be a clinically acceptable minimum requirement with an approximately 5% risk of margin-related recurrence. K-ras mutation in the metastatic lesion was related to a poor patient outcome after liver resection.