Mulder W M, Stern P L, Stukart M J, de Windt E, Butzelaar R M, Meijer S, Adér H J, Claessen A M, Vermorken J B, Meijer C J, Wagstaff J, Scheper R J, Bloemena E
Departments of Pathology, Surgery, and Oncology, Free University Hospital, 1081 HV Amsterdam, The Netherlands.
Clin Cancer Res. 1997 Nov;3(11):1923-30.
The purpose of this study was to investigate the prognostic value of the expression of intercellular adhesion molecule 1 (ICAM-1), leukocyte function antigen 3 (LFA-3), human leukocyte differentiation antigen (HLA)-ABC, HLA-DR, and 5T4 with regard to disease-free survival in Dukes' B and C colorectal carcinoma patients. Forty-one patients (28 Dukes' B and 13 Dukes' C) were entered into this study. Immunocytochemistry was performed on cytospin preparations of enzymatically digested colorectal carcinoma cell suspensions. The frequency of metastases and the duration of disease-free survival were compared between the 25% lowest expressers and the 75% remaining patients for ICAM-1, LFA-3, HLA-ABC, and HLA-DR, and between the 25% highest expressers and the 75% remaining patients for 5T4. Low numbers of ICAM-1-expressing tumor cells were associated with a shorter disease-free survival (P < 0. 001), independent of Dukes' stage. High numbers of 5T4-expressing tumor cells were associated with shorter disease-free survival in Dukes' B patients (P = 0.04). Cox proportional hazard analysis indicated that low numbers of ICAM-1(+) and high numbers of 5T4(+) cells were independent prognostic factors with relative risks of 13. 0 (P = 0.0002) and 4.7 (P = 0.02), respectively. The combination of 5T4 and ICAM-1 marker information identified subgroups of patients with a good (high ICAM-1) or poor (low ICAM-1/high 5T4) prognosis. Neither a lack of HLA-ABC and LFA-3 expression nor the presence of HLA-DR on the tumor cells gave additional prognostic information. These findings demonstrate that low ICAM-1 and high 5T4 expression on tumor cells are prognostic markers, additional to Dukes' stage, for reduced disease-free survival in Dukes' B and C colorectal carcinoma patients.
本研究旨在探讨细胞间黏附分子1(ICAM-1)、白细胞功能抗原3(LFA-3)、人类白细胞分化抗原(HLA)-ABC、HLA-DR及5T4的表达对Dukes' B期和C期结直肠癌患者无病生存期的预后价值。41例患者(28例Dukes' B期和13例Dukes' C期)纳入本研究。对经酶消化的结直肠癌细胞悬液的细胞涂片制备物进行免疫细胞化学检测。比较ICAM-1、LFA-3、HLA-ABC和HLA-DR表达最低的25%患者与其余75%患者的转移频率和无病生存期,以及5T4表达最高的25%患者与其余75%患者的转移频率和无病生存期。表达ICAM-1的肿瘤细胞数量少与无病生存期缩短相关(P<0.001),与Dukes'分期无关。Dukes' B期患者中,表达5T4的肿瘤细胞数量多与无病生存期缩短相关(P = 0.04)。Cox比例风险分析表明,ICAM-1(+)细胞数量少和5T4(+)细胞数量多是独立的预后因素,相对风险分别为13.0(P = 0.0002)和4.7(P = 0.02)。5T4和ICAM-1标记信息的组合确定了预后良好(ICAM-1高表达)或预后不良(ICAM-1低表达/5T4高表达)的患者亚组。肿瘤细胞上HLA-ABC和LFA-3表达缺失以及HLA-DR的存在均未提供额外的预后信息。这些发现表明,肿瘤细胞上ICAM-1低表达和5T4高表达是Dukes' B期和C期结直肠癌患者无病生存期缩短的预后标志物,是除Dukes'分期之外的额外指标。