荧光原位杂交检测乳腺癌HER2基因状态

Evaluation of HER2 gene expression status in breast cancer by fluorescence in-situ hybridization

目的探讨荧光原位杂交(FISH),与免疫组织化学(IHC)染色(3+)和(2+)检测HER2基因状态的结果的一致性、导致两者差异的可能原因及FISH检测HER2基因状态的必要性和可行性。方法采用PathVysionTM探针试剂盒,以FISH方法,对28例IHCEnVision法染色分别为(3+)、(2+)、(1+)和阴性(-)的乳腺癌石蜡切片标本进行HER2基因状态的检测。结果HER2表达(3+)的12例标本中,10例HER2基因扩增,其中2例为17号染色体多体,另2例无扩增的病例均为多体;IHC为(2+)的10例标本中,7例为HER2基因扩增,其中1例为多体,另3例无扩增病例中2例为多体;IHC为(1+)的3例标本均无HER2基因扩增,其中1例为多体;IHC(-)的3例标本均无基因扩增,其中1例为多体。结论IHC是初步筛查HER2状态的首选方法;因IHC(2+)与FISH检测结果差异较大,所以这类患者应做FISH确诊;IHC(3+)存在假阳性,主要原因可能是由于17号染色体非整倍体,必要时这类患者也应做FISH。

Objective To deduce the protocol, scoring criteria and interpretive guidelines for assessment of HER2 gene expression status by fluorescence in-situ hybridization （FISH） and to compare the results with those obtained by immunohistochemistry. Methods The HercepTestTM kit from Dako Cytomation was employed for immunohistochemistry. FISH for HER2 gene expression status was performed using PathVysionTM DNA probe kit on the archival paraffin-embedded sections of breast cancer tissues from 28 Chinese female patients with immunohistochemical staining scores of （3 ＋ ） , （ 2 ＋ ） , （ 1 ＋ ） and 0. Results Ten of the 12 patients with score （3 ＋ ） by immunohistochemistry were positive for HER2 by FISH, with 2 cases being polysomy. Two other cases with FISH-negative were also shown to be polysomy. Seven of the 10 patients with score （2 ＋ ） by immunohistochemistry showed HER2 gene amplification, with 1 case being polysomy. Two of the remaining 3 cases, which were FISH-negative, were shown to be polysomy. All the patients with scores （ 1 ＋ , number = 3） or 0 （ number = 3 ） by immunohistochemistry failed to show amplification. One case of polysomy was noted in either group. Conclusions Immunohistochemistry is useful as an initial screening tool for HER2 expression status. Because of the obvious discrepancies between protein expression and gene amplification, patients with score （2 ＋ ） by immunohistochemistry should undergo FISH testing as well. FISH is also required in selected examples with score （3 ＋ ） immunohistochemical results, especially in those with false-positive immunohistochemistry due to chromosome 17 aneuploidy.