Analysis of HER2 expression in primary urinary bladder carcinoma and corresponding metastases
Analysis of HER2 expression in primary urinary bladder carcinoma and corresponding metastases
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DOI：
10.1111/j.1464-410x.2005.05452.x
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发表时间：
2005-05-01
影响因子：
4.5
通讯作者：
Malmström, PU
中科院分区：
文献类型：
--
作者：
Gårdmark, T;Wester, K;Malmström, PU
为探讨HER2受体在膀胱移行细胞癌原发灶和转移灶中的表达情况，采用两种不同的染色方法和两种不同的评分方法，探讨HER2受体作为系统性抗HER2核素治疗靶点的可能性。应用两种不同的免疫组织化学方法检测90例原发膀胱癌及其相应转移灶中HER2的表达。切片首先用商业上可用的乳腺癌检测试剂盒(HercepTest(R)，达科，格洛斯特鲁普，丹麦)染色。然后用改进的HercepTest程序对平行切片进行染色。两个不同的评估标准进行了比较；HercepTest分数要求>；=10%染色的肿瘤细胞(如乳腺癌)，以及建议的目标分数，要求>；67%染色的肿瘤细胞。后一种评分被认为是HER2靶向放射性核素治疗的首选。使用HercepTest试剂盒，Target评分给出的阳性原发肿瘤和转移瘤的比例低于HercepTest评分。改良的HercepTest染色程序和Target评分在80%的原发肿瘤和62%的转移瘤中显示出较高的HER2值，明显高于HercepTest染色和评分。随着距离原发肿瘤距离的增加，HER2的阳性表达显著降低。在评估的9个前哨淋巴结转移中，除1个外，其余均为HER2阳性。考虑到所有的区域转移，74%是阳性的，在远处转移中，47%；72%的阳性原发肿瘤患者在他们的转移中也表达HER2。当结合改良的HercepTest和定制的评估标准时，更多的HER2阳性肿瘤被诊断出来。HER2在远处转移中的下调程度明显高于区域转移。在未来转移性膀胱癌的治疗中，HER2靶向治疗可能是其他方法的替代或补充。
To evaluate the expression of HER2 receptors (previously reported to be over-expressed in malignant urothelium) in both primary tumours and metastases of transitional cell cancer, using two different staining methods and two different scoring techniques, considering the potential use of these receptors as targets for planned systemic anti-HER2 nuclide-based treatment.HER2 expression was evaluated with two different immunohistochemical methods in 90 patients with primary urinary bladder cancer tumours and corresponding metastases. Sections were first stained with the commercially available breast cancer test kit (HercepTest (R), Dako, Glostrup, Denmark). Parallel sections were then stained with a modified HercepTest procedure. Two different evaluation criteria were compared; the HercepTest score that requires >= 10% stained tumour cells (as for breast cancer) and a proposed 'Target score' that requires > 67% stained tumour cells. The latter score is assumed to be preferable for HER2-targeted radionuclide therapy.Using the HercepTest kit, the Target score gave lower fractions of positive primary tumours and metastases than the HercepTest score. The modified HercepTest staining procedure and Target score gave high HER2 values in 80% of primary tumours and 62% of metastases, which is considerably more than that obtained with the HercepTest staining and score. There was a significant decrease in HER2 positivity with increasing distance from the primary tumour. In nine sentinel-node metastases assessed, all but one were HER2-positive. Considering all regional metastases, 74% were positive, and of distant metastases, 47%; 72% of the patients with positive primary tumours also expressed HER2 in their metastases.When combining the modified HercepTest with customised evaluation criteria, more HER2-positive tumours were diagnosed. The degree of HER2 down-regulation was significantly higher in distant than in regional metastases. HER2-targeted therapy may be an alternative or complementary to other methods in the future treatment of metastatic urinary bladder carcinoma.