HER2 status in breast cancer of Chinese women: a study of 1170 cases using fluorescence in-situ hybridization / 中华病理学杂志

ABSTRACT

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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).</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>