脑脊液细胞学在与乳腺癌继发中枢神经系统转移中肿瘤标志物活性比较时的诊断价值

Diagnostic value of cerebrospinal fluid cytology in comparison with tumor marker activity in central nervous system metastases secondary to breast cancer.

作者信息

Bach F, Bjerregaard B, Sölétormos G, Bach F W, Horn T

机构信息

Department of Oncology, Herlev Hospital, University of Copenhagen, Denmark.

出版信息

Cancer. 1993 Oct 15;72(8):2376-82. doi: 10.1002/1097-0142(19931015)72:8<2376::aid-cncr2820720814>3.0.co;2-6.

DOI:10.1002/1097-0142(19931015)72:8<2376::aid-cncr2820720814>3.0.co;2-6

PMID:8402452

Abstract

BACKGROUND

Central nervous system (CNS) metastases occur in approximately 35% of patients with breast cancer. Parenchymal brain metastases (MET) remain undetected in a large proportion of patients, and only 50% of patients with leptomeningeal carcinomatosis (MC) are diagnosed in vivo.

METHODS

Cytology and activity of the tumor markers tissue polypeptide antigen (TPA) and creatine kinase-BB isoenzyme (CK-BB) were evaluated in the cerebrospinal fluid (CSF) in 71 consecutive patients with breast cancer suspected for CNS metastases.

RESULTS

Forty-three patients had no CNS metastases, 12 patients had MET, 5 patients had both MET and MC, and 11 patients had MC alone. Seven of the patients with MC had an intracerebroventricular (ICV) reservoir inserted, and an additional 70 ICV CSF samples from these patients were obtained. In CSF obtained by lumbar puncture, 11% of the samples were classified as "suspicious for malignancy," but a very limited interobserver variability was demonstrated (Kappa test value, 0.81; 95% confidence limits, 0.67-0.95%). Fifty-one percent of the ICV CSF samples were classified as "suspicious for malignancy" (Kappa test value, 0.58; 95% confidence limits, 0.34-0.82%). TPA and CK-BB were both measured in 101 CSF specimens (61 from lumbar puncture and 40 ICV samples). The differences between patients with and without CNS metastases were significantly different according to TPA (P < 0.00001) and CK-BB (P < 0.00003; Mann-Whitney test). The sensitivity and predictive value of a negative test for having any CNS metastases (in case of elevated values of either TPA or CK-BB or both) were 85% (95% confidence limits, 65-96%) and 90% (95% confidence limits, 76-97%), respectively. In addition, a significant correlation between TPA and CK-BB was demonstrated in CSF from lumbar puncture (Spearmans-Rho, 0.49; P < 0.0001) and ICV (Spearmans-Rho, 0.37; P < 0.02).

CONCLUSIONS

Cytologic evaluation of CSF obtained by lumbar punctures is a reliable procedure. In CSF from ICV reservoirs, cytologic evaluation is of limited use, but CK-BB and TPA is of potential value.

摘要

背景

中枢神经系统（CNS）转移发生在约35%的乳腺癌患者中。很大一部分患者的脑实质转移（MET）仍未被发现，只有50%的柔脑膜癌病（MC）患者在体内被诊断出来。

方法

对71例疑似CNS转移的连续乳腺癌患者的脑脊液（CSF）进行肿瘤标志物组织多肽抗原（TPA）和肌酸激酶-BB同工酶（CK-BB）的细胞学及活性评估。

结果

43例患者无CNS转移，12例患者有MET，5例患者既有MET又有MC，11例患者仅有MC。7例MC患者插入了脑室内（ICV）储液器，并从这些患者中额外获取了70份ICV脑脊液样本。在通过腰椎穿刺获取的脑脊液中，11%的样本被归类为“可疑恶性”，但观察者间差异非常有限（Kappa检验值，0.81；95%置信区间，0.67 - 0.95%）。51%的ICV脑脊液样本被归类为“可疑恶性”（Kappa检验值，0.58；95%置信区间，0.34 - 0.82%）。在101份脑脊液标本（61份来自腰椎穿刺，40份ICV样本）中均检测了TPA和CK-BB。根据TPA（P < 0.00001）和CK-BB（P < 0.00003；曼-惠特尼检验），有无CNS转移的患者之间差异显著。对于有任何CNS转移（TPA或CK-BB或两者值升高的情况），阴性检测的敏感性和预测值分别为85%（95%置信区间，65 - 96%）和90%（95%置信区间，76 - 97%）。此外，在腰椎穿刺脑脊液（Spearmans-Rho，0.49；P < 0.0001）和ICV脑脊液（Spearmans-Rho，0.37；P < 0.02）中，TPA和CK-BB之间存在显著相关性。