Pujol J L, Grenier J, Daurès J P, Daver A, Pujol H, Michel F B
Clinique des Maladies Respiratoires, Université de Montpellier, Hôpital Aiguelongue, France.
Cancer Res. 1993 Jan 1;53(1):61-6.
Cytokeratin 19 is a subunit of cytokeratin intermediate filament expressed in simple epithelia and their malignant counterparts. Therefore, it is expressed by respiratory epithelium cells and has been detected in lung cancer specimens. An immunoradiometric assay was used to detect a fragment of the cytokeratin 19, referred to as CYFRA 21-1, in the serum of 165 patients with histologically proved lung cancer (128 non-small cell and 37 small cell lung cancers). This prospective study was conducted to evaluate the reliability of this immunoradiometric assay and to identify the relationship between serum CYFRA 21-1 and different features of lung cancer including prognosis. The minimal detectable concentration detected by this assay was 0.06 ng/ml. The reliability of the immunoradiometric assay was demonstrated by the linear relationship between CYFRA 21-1 measurement and dilution of the serum, the reproducibility of the dosage in intraassay and interassay, and the high sensitivity of the method in discriminating low CYFRA 21-1 concentrations. Using a threshold of 3.6 ng/ml, sensitivity and specificity were 0.52 and 0.87, respectively. The sensitivity of the marker was highest in squamous cell carcinoma and lowest in small cell carcinoma. In non-small cell lung cancer patients, the marker varied significantly according to both stage of the disease (Kruskal-Wallis, 13.7; P < 0.005) and performance status (Kruskal-Wallis, 9.16; P < 0.05) inasmuch as a high serum CYFRA 21-1 level was associated with advanced stages, mediastinal lymph nodes, and poor performance status. Consequently, the marker was significantly lower in patients who were operated upon when compared with unresectable ones. Lung cancer patients with serum CYFRA 21-1 over 3.6 ng/ml proved to have a significantly shorter overall survival than those with a normal serum level (log rank, P = 0.007; Wilcoxon, P = 0.001). The negative prognostic effect of CYFRA 21-1 was highly significant in squamous cell carcinomas whereas it was nonsignificant for the other histologies. In Cox's model analysis, performance status, stage grouping, and CYFRA 21-1 were the only significant determinants of survival. This study supports the use of the serum fragment of cytokeratin subunit 19 CYFRA 21-1 as an independent prognostic marker of squamous cell carcinoma of the lung.
细胞角蛋白19是细胞角蛋白中间丝的一个亚基，在单层上皮及其恶性对应物中表达。因此，它由呼吸道上皮细胞表达，并已在肺癌标本中检测到。采用免疫放射分析方法检测了165例经组织学证实的肺癌患者（128例非小细胞肺癌和37例小细胞肺癌）血清中的细胞角蛋白19片段，即CYFRA 21-1。本前瞻性研究旨在评估该免疫放射分析方法的可靠性，并确定血清CYFRA 21-1与肺癌不同特征（包括预后）之间的关系。该检测方法的最低可检测浓度为0.06 ng/ml。CYFRA 21-1测量值与血清稀释度之间的线性关系、批内和批间剂量的可重复性以及该方法区分低CYFRA 21-1浓度的高灵敏度，证明了免疫放射分析方法的可靠性。以3.6 ng/ml为临界值，灵敏度和特异性分别为0.52和0.87。该标志物在鳞状细胞癌中的灵敏度最高，在小细胞癌中最低。在非小细胞肺癌患者中，该标志物根据疾病分期（Kruskal-Wallis检验，13.7；P<0.005）和体能状态（Kruskal-Wallis检验，9.16；P<0.05）有显著差异，因为血清CYFRA 21-1水平升高与晚期、纵隔淋巴结和体能状态差相关。因此，与无法切除的患者相比，接受手术治疗的患者该标志物明显较低。血清CYFRA 21-1超过3.6 ng/ml的肺癌患者的总生存期明显短于血清水平正常的患者（对数秩检验，P = 0.007；Wilcoxon检验，P = 0.001）。CYFRA 21-1的负面预后作用在鳞状细胞癌中非常显著，而在其他组织学类型中则不显著。在Cox模型分析中，体能状态、分期分组和CYFRA 21-1是生存的唯一显著决定因素。本研究支持将细胞角蛋白亚基19的血清片段CYFRA 21-1用作肺鳞状细胞癌的独立预后标志物。
