Colorectal Carcinoma liver Metastases : Immunohistochemical Detection of Hepatic Micrometastases Using Monoclonal Anticytokeratin Antibody

背景：结直肠癌的肝转移常在切除后复发，肝微转移很可能在这种复发的发生中起重要作用。本研究的目的是探讨免疫组织化学方法检测结直肠癌肝微转移的可行性及其临床意义。方法：1981年1月至2003年12月，129例结直肠癌肝转移根治性切除患者。从每个患者最大的肝转移灶的前缘切取多个组织切片，用细胞角蛋白-20抗体染色以检测肝微转移灶，肝微转移灶被定义为围绕优势转移灶周围的离散的微小癌变。免疫组织化学Ki-67染色检测肝微转移灶中肿瘤细胞增殖情况，作为肿瘤细胞活性的指标。T…中位随访时间127个月。结果：正常肝细胞和肝内胆管上皮细胞角蛋白-20染色均为阴性，而最大的肝肿瘤细胞角蛋白-20染色阳性114例(88%)。在细胞角蛋白-20阳性的114例肝肿瘤患者中，77例(68%)经免疫组织化学检测发现肝脏微转移灶(共211个病灶)。肝微转移的出现与大量的宏观肝转移有关(P=0.002)，与无肝微转移的患者相比，有肝微转移的患者肝内复发的概率更高(P&lt；0.001)。此外，有肝微转移的患者的生存率(10年累计生存率为21%)比无肝微转移的患者(10年累计生存率为66%)更差(P&lt；0.001)。大多数肝微转移灶Ki-67染色阳性(189/211，90%)。结论：免疫组织化学检测肝微转移灶在结直肠癌肝转移中是可行的。肝脏微转移表明肝脏广泛受累，因此预示着肝切除术后肝内复发的风险增加，患者预后较差。肝微转移中的大多数肿瘤细胞似乎都是存活的。较少

BACKGROUND : Hepatic metastases from colorectal carcinoma frequently recur after resection and hepatic micrometastases most likely are important in the development of such recurrences. The objectives of the current study were to assess the feasibility of the immunohistochemical detection of hepatic micrometastases from colorectal carcinoma and to determine their clinical significance.METHODS : From January 1981 through December 2003,a total of 129 patients underwent curative hepatic resection for colorectal carcinoma metastases. Multiple tissue sections were cut from the advancing margin of the largest hepatic metastasis in each patient and were stained with an antibody against cytokeratin-20 to detect hepatic micrometastases, which were defined as discrete microscopic cancerous lesions surrounding the dominant metastasis. Proliferation of tumor cells in the hepatic micrometastases was assessed immunohistochemically with Ki-67 staining as an indicator of viability of the tumor cells. T … More he median follow-up period was 127 months.RESULTS : Normal hepatocytes and intrahepatic bile duct epithelia stained negative for cytokeratin-20 in all patients, whereas the largest hepatic tumors stained positive in 114 patients (88%). Among the 114 patients with hepatic tumors that were positive for cytokeratin-20,hepatic micrometastases (a total of 211 lesions) were found immunohistochemically in 77 patients (68%). The presence of hepatic micrometastases was associated with a larger number of macroscopic hepatic metastases (P=0.002) and patients with hepatic micrometastases were found to demonstrate a higher probability of intrahepatic recurrence (P<0.001) compared with those patients without hepatic micrometastases. In addition, patients with hepatic micrometastases demonstrated a worse survival (cumulative 10-year survival rate of 21%) compared with those patients without hepatic micrometastases (cumulative 10-year survival rate of 66%) (P<0.001). Most of the hepatic micrometastases detected (189 of 211 lesions,90%) stained positive for Ki-67.CONCLUSIONS : Immunohistochemical detection of hepatic micrometastases is feasible in patients with colorectal carcinoma liver metastases. Hepatic micrometastasis indicates widespread hepatic involvement and thus predicts an increased risk of intrahepatic recurrence after hepatic resection and a poorer patient prognosis. Most tumor cells in hepatic micrometastases appear to be viable. Less