Haddad Riad, Ogilvie Robert T, Croitoru Marina, Muniz Victoria, Gryfe Robert, Pollet Aaron, Shanmugathasan Preshanthini, Fitzgerald Timothy, Law Calvin H L, Hanna Sherif S, Jothy Serge, Redston Mark, Gallinger Steven, Smith Andrew J
Sunnybrook and Women's Health Sciences Centre, T-Wing, Room T2-057, 2075 Bayview Avenue, Toronto, Ontario, Canada M4N 3M5.
Ann Surg Oncol. 2004 Nov;11(11):977-82. doi: 10.1245/ASO.2004.03.585. Epub 2004 Oct 15.
Two distinct genetic mutational pathways characterized by either chromosomal instability or high-frequency microsatellite instability (MSI-H) are currently recognized in the pathogenesis of colorectal cancer (CRC). Recently, it has been shown that patients with primary CRC that displays MSI-H have a significant, stage-independent, multivariate survival advantage. Untreated CRC hepatic metastases are incurable and are associated with a median survival of 4 to 12 months. Conversely, surgical resection in selected patients results in a 20% to 50% cure rate. The aim of this study was to investigate the prognostic importance of MSI-H in patients undergoing resection of hepatic CRC metastases.
DNA was extracted from paraffin-embedded, resected metastatic CRC liver lesions and corresponding normal liver parenchyma from 190 patients. MSI-H status was determined by polymerase chain reaction-based evaluation of the noncoding mononucleotide repeats BAT-25 and BAT-26.
MSI was detected in tumors from 5 (2.7%) of the 190 CRC patients. All MSI-H tumors were in patients with node-positive CRC primary tumors. The median survival after hepatic resection of MSI-H and non-MSI-H tumors was 67 and 61 months, respectively (P = .9).
These data suggest that MSI-H is not a common feature in resected CRC liver metastases and do not suggest a role for MSI in stratifying good versus poor prognosis in these patients.
目前在结直肠癌(CRC)发病机制中已确认存在两种不同的基因突变异质性途径,其特征分别为染色体不稳定或高频微卫星不稳定(MSI-H)。最近研究表明,原发性CRC表现为MSI-H的患者具有显著的、与分期无关的多因素生存优势。未经治疗的CRC肝转移无法治愈,中位生存期为4至12个月。相反,部分患者接受手术切除后治愈率可达20%至50%。本研究旨在探讨MSI-H在接受CRC肝转移灶切除患者中的预后重要性。
从190例患者石蜡包埋的切除性CRC肝转移灶及相应正常肝实质中提取DNA。通过基于聚合酶链反应对非编码单核苷酸重复序列BAT-25和BAT-26的评估来确定MSI-H状态。
190例CRC患者中有5例(2.7%)肿瘤检测到MSI。所有MSI-H肿瘤患者的原发性CRC肿瘤均有淋巴结转移。MSI-H和非MSI-H肿瘤肝切除术后的中位生存期分别为67个月和61个月(P = 0.9)。
这些数据表明MSI-H并非切除的CRC肝转移灶的常见特征,且不提示MSI在这些患者的预后分层中具有区分预后好坏的作用。