摘要
目的探索中国大陆女性乳腺癌 HER2蛋白过表达人群中 HER2基因状态、蛋白表达与基因扩增的一致性、17号染色体非整体性的发生情况及其意义。方法采用 PathVysion^(TM)探针试剂盒,以荧光原位杂交(FISH)方法,分析经免疫组织化学(IHC)方法(HercepTest^(TM)试剂盒)确认的120例 HER2蛋白表达阳性(IHC 2+者42例,IHC 3+者78例)的乳腺癌石蜡切片标本的 HER2基因状态和17号染色体非整体性的发生率。结果 HER2表达 IHC 2+的标本中,基因扩增率76.19%(32/42),其中低度扩增(比值2～4)26.19%(11/42),中度扩增(比值4～10)41.62%(20/42),高度扩增(比值>10)2.38%(1/42);IHC 3+的标本中,基因扩增率91.03%(71/78),其中低度扩增11.54%(9/78),中度扩增61.54%(48/78),高度扩增17.95%(14/78)。全部病例中具有17号染色体非整体性者69.17%(83/120),包括亚二体性(17号染色体平均数≤1.75)11.67%(14/120)、低多体性(17号染色体平均数2.26～3.75)43.33%(52/120)和高多体性(17号染色体平均数≥3.76)14.17%(17/120)。IHC 2+病例中17号染色体非整体性59.52%(25/42),包括亚二体性7.14%(3/42)、低多体性42.86%(18/42)和高多体性9.52%(4/42);IHC 3+病例中17号染色体非整体性74.36%(58/78),包括亚二体性14.10%(11/78)、低多体性43.59%(34/78)和高多体性16.67%(13/78)。IHC 2+者 FISH 阳性以 HER2基因中、低度扩增为主,而 IHC 3+者则呈中、高度基因扩增的趋势,两者差异有统计学意义(P=0.0003)。IHC 3+中,7例 FISH 阴性中6例有17号染色体非整体性;IHC 2+中,10例 FISH 阴性中5例有17号染色体非整体性。结论在本组中国大陆女性乳腺癌人群中,IHC 3+与 FISH 阳性的一致性较高;IHC 2+者 FISH 阳性率高于国外研究者的数据;HER2蛋白阳性乳腺癌中17号染色体非整体性发生比例较高;IHC 2+和3+者都具亚二体性、低多体性和高多体性特征,且两者均以低多体性为常见;IHC 2+者的 HER2基因扩增多为中、低度扩增,而 IHC3+中 FISH 阳性者则以高比值者居多。IHC 3+而 FISH 阴性的主要原因为17号染色体非整体性。
Objective 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. Methods 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. Results 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 - 4）, 20 cases with moderate amplification （ratio 4 - 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 ≤ 1.75） , 52 cases （43.33%） showed low polysomy （ chromosome 17 copy number per cell = 2. 26 - 3.75） and 17 cases （ 14. 17% ） showed high polysomy （chromosome 17 copy number per cell ≥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 ＋ andFISH-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. Conclusions 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.
出处
《中华病理学杂志》
CAS
CSCD
北大核心
2006年第10期584-588,共5页
Chinese Journal of Pathology
基金
国家"十五"攻关课题基金(2004BA720A08)
关键词
乳腺肿瘤
基因
ERBB-2
染色体
人
17对
免疫组织化学
原位杂交
荧光
Breast neoplasms
Genes, erbB-2
Chromosomes, human, pair 17
Immunohistochemistry
In situ hybridization, Fluorescence
