Diefenbach Catherine S M, Shah Zharna, Iasonos Alexia, Barakat Richard R, Levine Douglas A, Aghajanian Carol, Sabbatini Paul, Hensley Martee L, Konner Jason, Tew William, Spriggs David, Fleisher Martin, Thaler Howard, Dupont Jakob
Gynecologic Medical Oncology, Department of Medicine, Howard 903, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Gynecol Oncol. 2007 Feb;104(2):435-42. doi: 10.1016/j.ygyno.2006.08.028. Epub 2006 Oct 4.
YKL-40 is a secreted glycoprotein of the chitinase family that has been previously described as a diagnostic and prognostic marker for a number of cancers, including epithelial ovarian cancer. In this study, we examined the frequency of serum elevation as well as the diagnostic and prognostic significance of this serum marker in endometrial cancer.
Preoperative serum levels of YKL-40 and CA125 were evaluated by enzyme-linked immunosorbent assay (ELISA) for all endometrial cancer patient samples (34) available in the Memorial Sloan-Kettering Cancer Center Gynecology Service Tissue Bank between the years 1987 and 2002, and compared to a cohort of normal individuals. A YKL-40 value of 61 ng/mL has previously been determined to represent the upper limit of normal. YKL-40 values were correlated with clinical characteristics, including patient age, tumor grade, histology, clinical stage, and clinical outcome (progression-free survival [PFS] and overall survival [OS]).
YKL-40 was elevated (>61 ng/mL) in 26 (76%) of 34 endometrial cancer patients compared with elevations of CA125 in 21 (62%) of 34 patients (P=0.09). Twenty-eight (82%) of all 34 patients had elevations of either CA125 or YKL-40 or both; 16 (89%) of 18 advanced-stage endometrial cancer patients had elevation of at least one of these two markers. Median preoperative YKL-40 value was 137 ng/mL (range, 22-1738 ng/mL) for endometrial cancer patients compared with 28 ng/mL (range, 15-72 ng/mL) for normal healthy subjects (P<0.0001). There was no statistically significant association of YKL-40 with patient age, tumor grade, histology, or stage. Elevation of YKL-40 (>80 ng/mL) was correlated with poor clinical outcome in univariate analysis, but was not demonstrated in multivariate analysis. At 5 years' follow-up, the PFS rate was 80% for patients with YKL-40<80 ng/mL compared with 43% for patients with YKL-40>80 ng/mL (P=0.004). The 5-year OS rate for patients with YKL-40<80 ng/mL was 79% compared with 48% for patients with YKL-40>80 ng/mL (P=0.047).
Preoperative serum YKL-40 is frequently elevated and may represent a novel marker for the detection of endometrial cancer and the identification of high-risk subsets of patients with worse clinical outcome. Further investigation of this promising endometrial cancer marker in larger studies is warranted.
YKL-40是一种几丁质酶家族的分泌型糖蛋白，此前已被描述为包括上皮性卵巢癌在内的多种癌症的诊断和预后标志物。在本研究中，我们检测了子宫内膜癌患者血清中YKL-40升高的频率以及该血清标志物的诊断和预后意义。
采用酶联免疫吸附测定（ELISA）法评估1987年至2002年间纪念斯隆凯特琳癌症中心妇科服务组织库中所有可用的34例子宫内膜癌患者样本术前血清YKL-40和CA125水平，并与一组正常个体进行比较。此前已确定YKL-40值为61 ng/mL代表正常上限。YKL-40值与临床特征相关，包括患者年龄、肿瘤分级、组织学、临床分期及临床结局（无进展生存期[PFS]和总生存期[OS]）。
34例子宫内膜癌患者中，26例（76%）YKL-40升高（>61 ng/mL），而34例患者中21例（62%）CA125升高（P = 0.09）。34例患者中28例（82%）CA125或YKL-40或两者均升高；18例晚期子宫内膜癌患者中有16例（89%）至少有这两种标志物之一升高。子宫内膜癌患者术前YKL-40中位数为137 ng/mL（范围22 - 1738 ng/mL），而正常健康受试者为28 ng/mL（范围15 - 72 ng/mL）（P < 0.0001）。YKL-40与患者年龄、肿瘤分级、组织学或分期无统计学显著相关性。单因素分析中YKL-40升高（>80 ng/mL）与不良临床结局相关，但多因素分析未证实。随访5年，YKL-40<80 ng/mL患者的PFS率为80%，而YKL-40>80 ng/mL患者为43%（P = 0.004）。YKL-40<80 ng/mL患者的5年OS率为79%，而YKL-40>80 ng/mL患者为48%（P = 0.047）。
术前血清YKL-40常升高，可能是检测子宫内膜癌及识别临床结局较差的高危患者亚组的新型标志物。有必要在更大规模研究中对这种有前景的子宫内膜癌标志物进行进一步研究。
