Webb A, Scott-Mackie P, Cunningham D, Norman A, Andreyev J, O'Brien M, Bensted J
Cancer Research Campaign Section of Medicine, Royal Marsden Hospital, Sutton, Surrey, U.K.
Ann Oncol. 1995 Jul;6(6):581-7. doi: 10.1093/oxfordjournals.annonc.a059248.
Evaluation of the prognostic significance of a group of tumour markers and their ability to predict response to chemotherapy may allow better targeting of palliative treatment in advanced colorectal cancer.
Using a prospectively acquired database of 377 patients (pts) with advanced colorectal adenocarcinoma, the prognostic significance of serum CEA (342 pts), beta HCG (203 pts), AFP (208 pts), CA125 (150 pts), CA-19-9 (76 pts) as well as C-erb B-2 (197 pts). Serum markers were taken prior to 5-FU based chemotherapy and immunohistochemistry was performed on diagnostic samples
Tumour markers of poor prognostic significance in the univariate analysis were CEA > or = 5 micrograms/l (p = 0.006; median survival (MS 59 weeks vs 38 weeks) and CA125 > or = 35 U/ml (p = 0.01 MS 51 weeks vs. 30 weeks). Tumour markers elevated at greater than 10 times the normal value which correlated with a poor prognosis were CEA (p = 0.001; MS 47 weeks vs. 35 weeks), Serum beta HCG (p < 0.0001; MS 44 weeks vs. 7 weeks) and CA125 (p < 0.0001; MS 38 weeks vs. 15 weeks). Poor performance status ( > 2) and poorly differentiated tumour histology were also correlated to poor survival. In the multivariate analysis, tumour markers of independent poor prognosis were CEA > or = 5 micrograms/l (Hazard Ratio (HR) 1.8; 95% Confidence Internal (CI) 2.8-1.2), CEA > or = 50 micrograms/l (HR 1.6; CI 2.1-1.2), CA125 > or = 35 U/ml (HR 1.5; CI 2.3-1.0), CA 125 > or = 350 U/ml (HR 5.0; CI 9.6-2.6) and serum BHCG > or = 0 IU/l (HR 11.7; CI 30-4.5). Poor performance status (HR 6.7-5.0) and poorly differentiated histology (HR 2.8-1.0) were the other important factors in the model. No pretreatment tumour marker correlated with response to chemotherapy.
This is the largest prognostic study of each tumour marker in advanced disease and it clarifies previous conflicting reports. Serum AFP, CA19-9 and immunohistochemical stains beta HCG and C-erb B-2 have no prognostic significance. Serum CEA, beta HCG, CA125 in advanced colorectal cancer prior to chemotherapy do convey an independent poor prognosis which may reflect not just tumour burden but aggressive biology.
评估一组肿瘤标志物的预后意义及其预测化疗反应的能力，可能有助于更好地针对晚期结直肠癌进行姑息治疗。
利用一个前瞻性收集的包含377例晚期结直肠腺癌患者的数据库，研究血清癌胚抗原（CEA，342例患者）、β-人绒毛膜促性腺激素（β-HCG，203例患者）、甲胎蛋白（AFP，208例患者）、糖类抗原125（CA125，150例患者）、糖类抗原19-9（CA-19-9，76例患者）以及C- erb B-2（197例患者）的预后意义。在基于5-氟尿嘧啶的化疗前采集血清标志物，并对诊断样本进行免疫组织化学检测。
单因素分析中预后意义差的肿瘤标志物为CEA≥5微克/升（p = 0.006；中位生存期（MS）59周对38周）和CA125≥35单位/毫升（p = 0.01；MS 51周对30周）。高于正常上限10倍且与预后差相关的肿瘤标志物为CEA（p = 0.001；MS 47周对35周）、血清β-HCG（p < 0.0001；MS 44周对7周）和CA125（p < 0.0001；MS 38周对15周）。体能状态差（>2）和肿瘤组织学分化差也与生存期短相关。多因素分析中，独立预后差的肿瘤标志物为CEA≥5微克/升（风险比（HR）1.8；95%置信区间（CI）2.8 - 1.2）、CEA≥50微克/升（HR 1.6；CI 2.1 - 1.2）、CA125≥35单位/毫升（HR 1.5；CI 2.3 - 1.0）、CA125≥350单位/毫升（HR 5.0；CI 9.6 - 2.6）以及血清β-HCG≥0国际单位/升（HR 11.7；CI 30 - 4.5）。体能状态差（HR 6.7 - 5.0）和组织学分化差（HR 2.8 - 1.0）是模型中的其他重要因素。没有预处理肿瘤标志物与化疗反应相关。
这是对晚期疾病中每种肿瘤标志物最大规模的预后研究，澄清了以往相互矛盾的报道。血清AFP、CA19-9以及免疫组织化学染色β-HCG和C- erb B-2无预后意义。化疗前晚期结直肠癌患者的血清CEA、β-HCG、CA125确实提示独立的预后差，这可能不仅反映肿瘤负荷，还反映侵袭性生物学行为。
