Anderhuber W, Steinschifter W, Gotschuli A, Schauenstein E, Schauenstein K
HNO-Univ. Klinik Graz.
Laryngorhinootologie. 1998 Oct;77(10):564-8. doi: 10.1055/s-2007-997027.
Until now no serological markers were available towards the diagnosis of squamous-cell carcinomas of the head and neck (HNSCC) particularly in the detection of posttherapeutic recurrent diseases and metastases. Previous reports described patients with malignant diseases of various tissues exhibiting a characteristic and highly significant alteration in the subclass composition of serum IgG, consisting of a reduction in %IgG1 and an increase of %IgG2. In this study we present for the first time results of this IgG-shift in patients suffering from HNSCC.
A total of 111 patients was investigated at our clinic, all suffering from primary, histopathologically verified squamous cell carcinomas of the head and neck. These patients were investigated as to %Ig G1/IgG2 prior to any treatment. A second group consisted of 35 patients with local recurrences, 15 patients with distant metastases and 27 patients without tumour at the time of investigation, who were in observation for 1 to 5 years after primary treatment (T0). Thirdly, a total of 33 patients was included who were afflicted with a variety of benign diseases of the head and neck, such as chronic rhinosinusitis, chronic tonsillitis and also lateral or median cysts of the neck. Data of the three groups were compared with those of 174 healthy volunteer controls. 5 ml blood were taken from a forearm vein and the quantitation of subclasses IgG1, IgG2 and total IgG was performed by affinity chromatography. The single values obtained with all experimental groups and healthy controls showed normal distribution for primary cancer patients versus healthy control. Accordingly, significant differences between mean values were calculated with the two-sided Students t-test, and cut-off values were calculated as the arithmetic means of mean values obtained from the groups to be compared. Diagnostic sensitivities and specificities were defined as percentages of patients with %IgG1 smaller, and of healthy controls with %IgG1 greater than the cut-off value.
We found a highly significant alteration in the subclass composition of serum IgG, consisting of a reduction in %IgG1 and an increase in %IgG2 in our HNSCC groups. The present data suggest the changes in %IgG1 and %IgG2 as a useful serological tumour marker to detect primary or recurrent and/or metastatic squamous-cell carcinomas of the head and neck.
The shift in %IgG1/%IgG2 exhibited diagnostic sensitivities and specificities comparable to, or--particularly at early tumour stages--by far higher than conventional serological tumour markers. Whereas conventional serological markers directly correspond to tumourogenically derived products, the shift in %IgG1/IgG2 represents an indirect marker, consisting of a change of the host's immune system due to the presence of malignant tumours.
到目前为止,尚无用于诊断头颈部鳞状细胞癌(HNSCC)的血清学标志物,特别是在检测治疗后复发疾病和转移方面。先前的报告描述了患有各种组织恶性疾病的患者血清IgG亚类组成出现特征性且高度显著的改变,即%IgG1降低和%IgG2升高。在本研究中,我们首次展示了HNSCC患者中这种IgG偏移的结果。
我们诊所共对111例患者进行了研究,所有患者均患有经组织病理学证实的原发性头颈部鳞状细胞癌。这些患者在接受任何治疗之前接受了%Ig G1/IgG2检测。第二组由35例局部复发患者、15例远处转移患者和27例在研究时无肿瘤的患者组成,这些患者在初次治疗(T0)后接受了1至5年的观察。第三,共纳入33例患有头颈部各种良性疾病的患者,如慢性鼻-鼻窦炎、慢性扁桃体炎以及颈部外侧或正中囊肿。将这三组的数据与174名健康志愿者对照的数据进行比较。从前臂静脉采集5毫升血液,通过亲和色谱法对IgG1、IgG2亚类和总IgG进行定量。所有实验组和健康对照获得的单个值显示,原发性癌症患者与健康对照呈正态分布。因此,使用双侧学生t检验计算平均值之间的显著差异,并将临界值计算为从要比较的组中获得的平均值的算术平均值。诊断敏感性和特异性定义为%IgG1小于临界值的患者百分比以及%IgG1大于临界值的健康对照百分比。
我们发现HNSCC组血清IgG亚类组成有高度显著的改变,即%IgG1降低和%IgG2升高。目前的数据表明,%IgG1和%IgG2的变化可作为检测原发性或复发性和/或转移性头颈部鳞状细胞癌的有用血清学肿瘤标志物。
%IgG1/%IgG2的偏移表现出与传统血清学肿瘤标志物相当的诊断敏感性和特异性,或者——特别是在肿瘤早期——远高于传统血清学肿瘤标志物。传统血清学标志物直接对应于肿瘤源性产物,而%IgG1/IgG2的偏移代表一种间接标志物,由恶性肿瘤的存在导致宿主免疫系统的变化组成。