Zeng Xuan, Liang Zhi-yong, Wu Sha-fei, Gao Jie, Zhou Wei-xun, Liu Tong-hua
Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Zhonghua Bing Li Xue Za Zhi. 2008 Sep;37(9):594-8.
To assess the prevalence of HER2 amplification according to HER2 and chromosome 17 copy numbers and HER2 FISH (fluorescence in-situ hybridization) ratio in breast cancer occurring in Chinese women.
Eleven hundreds and seventy cases of breast cancer occurring in Chinese women, who would be treated by trastuzumab and/or relevant chemotherapy based on HER2 status, were enrolled into the study. The formalin-fixed and paraffin-embedded tumor tissues were tested by FISH (PathVysion, Vysis).
Among the 1170 cases of breast cancer studied, 408 cases (34.87%) were FISH-negative, whereas 762 cases (65.13%) were FISH-positive, including 87 cases (87/762, 11.42%) with highly amplified HER2 gene (signals arranged in aggregates). As for the remaining 675 FISH-positive cases, 159 cases (23.56%) showed low amplification (HER2/CEP17 ratio = 2 to 4), 422 cases (62.52%) showed moderate amplification (ratio = 4 to 10) and 94 cases (13.93%) showed high amplification (ratio > 10) for HER2 gene. Only 14 of the 1170 cases (1.20%) had indeterminate results (ratio between 1.8 and 2.2), including 1.23% (5/408) borderline FISH-negative (ratio between 1.8 and 2.0) and 1.18% (9/762) borderline FISH-positive (ratio between 2.0 and 2.2). Our data showed that 73.00% (854/1170) of cases were chromosome 17 aneusomy, including 22.65% (265/1170) hypodisomy (chromosome 17 copy number per cell < or = 1.75), 38.38% (449/1170) low polysomy (chromosome 17 copy number per cell 2.26 to 3.75) and 11.97% (140/1170) high polysomy (chromosome 17 copy number per cell > or = 3.76). The frequency of chromosome 17 polysomy was 50.34%. In the FISH-positive subgroup, 23.88% (182/762) was disomy (chromosome 17 copy number per cell between 1.76 and 2.25), 24.15% (184/762) hypodisomy, 39.37% (300/762) low polysomy and 12.60% (96/762) high polysomy. The frequency of chromosome 17 polysomy in the FISH-positive subgroup was 51.97%. In the FISH-negative subgroup, 32.84% (134/408) were disomy, 19.85% (81/408) hypodisomy, 36.52% (149/408) low polysomy and 10.78% (44/408) high polysomy. The frequency of chromosome 17 polysomy in the FISH-negative subgroup was 47.30%. On the other hand, HER2 monoallelic deletion (HER2/CEP17 < or = 0.7) was observed in 2.39% of cases. Chromosome 17 monosomy was detected in 5.00% (38/762) and 4.41% (18/408) of HER2-positive and HER2-negative groups, respectively. A HER2 ratio of < 1.5 was noted in 32.30% of all cases (including 92.65% of HER2-negative cases), compared with 9.23% (108/1170) with ratio between 1.5 and 2.2.
The results show that a high amplification of HER2 gene is detected by FISH. Moderate amplification of HER2 gene and chromosome 17 polysomy are commonly seen in breast cancer patients in China Mainland. These findings may carry significant clinical and pathogenetic implication.
根据人表皮生长因子受体2（HER2）及17号染色体拷贝数和HER2荧光原位杂交（FISH）比值，评估中国女性乳腺癌中HER2基因扩增的发生率。
纳入1170例中国女性乳腺癌患者，这些患者将根据HER2状态接受曲妥珠单抗和/或相关化疗。采用FISH（PathVysion，Vysis）检测福尔马林固定、石蜡包埋的肿瘤组织。
在1170例研究的乳腺癌病例中，408例（34.87%）FISH检测为阴性，762例（65.13%）为阳性，其中HER2基因高度扩增（信号呈聚集排列）87例（87/762，11.42%）。其余675例FISH阳性病例中，159例（23.56%）显示低扩增（HER2/CEP17比值=2至4），422例（62.52%）显示中度扩增（比值=4至10），94例（13.93%）显示HER2基因高扩增（比值>10）。1170例中仅14例（1.20%）结果不确定（比值在1.8至2.2之间），包括1.23%（5/408）临界FISH阴性（比值在1.8至2.0之间）和1.18%（9/762）临界FISH阳性（比值在2.0至2.2之间）。我们的数据显示，73.00%（854/1170）的病例存在17号染色体非整倍体，包括22.65%（265/1170）亚二倍体（每个细胞17号染色体拷贝数≤1.75），38.38%（449/1170）低多倍体（每个细胞17号染色体拷贝数2.26至3.75）和11.97%（140/1170）高多倍体（每个细胞17号染色体拷贝数≥3.76）。17号染色体多倍体的发生率为50.34%。在FISH阳性亚组中，23.88%（182/762）为二倍体（每个细胞17号染色体拷贝数在1.76至2.25之间），24.15%（184/762）为亚二倍体，39.37%（300/762）为低多倍体，12.60%（96/762）为高多倍体。FISH阳性亚组中17号染色体多倍体的发生率为51.97%。在FISH阴性亚组中，32.84%（134/408）为二倍体，19.85%（81/408）为亚二倍体，36.52%（149/408）为低多倍体，10.78%（44/408）为高多倍体。FISH阴性亚组中17号染色体多倍体的发生率为47.30%。另一方面，2.39%的病例观察到HER2单等位基因缺失（HER2/CEP17≤0.7）。HER2阳性组和HER2阴性组中17号染色体单体分别在5.00%（38/762）和4.41%（18/408）中检测到。所有病例中32.30%观察到HER2比值<1.5（包括92.65%的HER2阴性病例），相比之下，9.23%（108/1170）的病例比值在1.5至2.2之间。
结果显示FISH检测到HER2基因高扩增。HER2基因中度扩增和17号染色体多倍体在中国大陆乳腺癌患者中常见。这些发现可能具有重要的临床和发病机制意义。
