Zeng Xuan, Liang Zhi-yong, Wu Sha-fei, Zhou Wei-xun, Gao Jie, Liu Tong-hua
Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China.
Zhonghua Bing Li Xue Za Zhi. 2006 Oct;35(10):584-8.
To study the HER2 gene status (by fluorescence in situ hybridization (FISH) in breast cancer with HER2 protein overexpression, the correlation between gene amplification and protein overexpression, as well as the rate and significance of chromosome 17 aneusomy.
One hundred and twenty archival cases of breast cancer with formalin-fixed and paraffin-embedded tumor tissues with 2+ (42 cases) and 3+ (78 cases) HER2 protein overexpression by immunohistochemistry (IHC, HercepTest, Dako) were tested by FISH (PathVysion, Vysis) for HER2 gene status. The rate of chromosome 17 aneusomy was also analyzed.
Amongst the 42 samples with IHC 2+, HER2 gene amplification was identified in 32 cases (76.19%), which included 11 cases with low amplification (ratio 2 approximately 4), 20 cases with moderate amplification (ratio 4 approximately 10) and 1 case with high amplification (ratio>10). Amongst the 78 samples with IHC 3+, HER2 gene amplification was identified in 71 cases (91.03%), which included 9 cases with low amplification, 48 cases with moderate amplification and 14 cases with high amplification. Chromosome 17 aneusomy was found in 83 cases (83/120, 69.17%), in which 14 cases (11.67%) showed hypodisomy (chromosome 17 copy number per cell<or=1.75), 52 cases (43.33%) showed low polysomy (chromosome 17 copy number per cell=2.26 approximately 3.75) and 17 cases (14.17%) showed high polysomy (chromosome 17 copy number per cell>or=3.76). Amongst the 42 cases with IHC 2+, 25 samples (59.52%) had chromosome 17 aneusomy, including 3 cases with hypodisomy, 18 cases with low polysomy and 4 cases with high polysomy. Amongst the 78 cases with IHC 3+, 58 samples (74.36%) had aneusomy 17, including 11 cases with hypodisomy, 34 cases with low polysomy and 13 cases with high polysomy. Most of IHC 2+ and FISH-positive cases had low or moderate HER2 gene amplification, while most of the IHC 3+ and FISH-positive cases had moderate or high gene amplification (P=0.0003). Six of the 7 samples with IHC 3+ and FISH-negativity had chromosome 17 aneusomy and 5 of the 10 samples with IHC 2+ and FISH-negativity had such aneusomy.
A high concordance rate is noted between IHC 3+ and FISH positive results. The rate of FISH positive in IHC 2+ patients was higher than reported in other studies. Low or moderate HER2 gene amplification in IHC 2+ and moderate or high gene amplification in IHC 3+ occurs quite frequently. Chromosome 17 aneusomy (including hypodisomy, low polysomy and high polysomy) is also a relatively common phenomenon in our cohort with HER2 overexpression, with predominance of low polysomy.
通过荧光原位杂交（FISH）研究HER2蛋白过表达的乳腺癌中HER2基因状态、基因扩增与蛋白过表达之间的相关性，以及17号染色体非整倍体的发生率和意义。
对120例经福尔马林固定、石蜡包埋的乳腺癌存档病例进行研究，这些病例经免疫组织化学（IHC，HercepTest，Dako）检测HER2蛋白过表达为2+（42例）和3+（78例），采用FISH（PathVysion，Vysis）检测HER2基因状态。同时分析17号染色体非整倍体的发生率。
在42例IHC 2+的样本中，32例（76.19%）检测到HER2基因扩增，其中低扩增（比值约2至4）11例，中度扩增（比值约4至10）20例，高扩增（比值>10）1例。在78例IHC 3+的样本中，71例（91.03%）检测到HER2基因扩增，其中低扩增9例，中度扩增48例，高扩增14例。83例（83/120，69.17%）发现17号染色体非整倍体，其中14例（11.67%）表现为亚二倍体（每细胞17号染色体拷贝数≤1.75），52例（43.33%）表现为低多倍体（每细胞17号染色体拷贝数=2.26至3.75），17例（14.17%）表现为高多倍体（每细胞17号染色体拷贝数≥3.76）。在42例IHC 2+的病例中，25例（59.52%）存在17号染色体非整倍体，包括亚二倍体3例，低多倍体18例，高多倍体4例。在78例IHC 3+的病例中，58例（74.36%）存在17号染色体非整倍体，包括亚二倍体11例，低多倍体34例，高多倍体13例。大多数IHC 2+且FISH阳性的病例HER2基因呈低或中度扩增，而大多数IHC 3+且FISH阳性的病例基因呈中度或高度扩增（P=0.0003）。7例IHC 3+且FISH阴性的样本中有6例存在17号染色体非整倍体，10例IHC 2+且FISH阴性的样本中有5例存在这种非整倍体。
IHC 3+与FISH阳性结果之间的一致性率较高。IHC 2+患者中FISH阳性率高于其他研究报道。IHC 2+时HER2基因低或中度扩增以及IHC 3+时基因中度或高度扩增较为常见。17号染色体非整倍体（包括亚二倍体、低多倍体和高多倍体）在我们HER2过表达的队列中也是一种相对常见的现象，以低多倍体为主。
