摘要
目的：探讨乳腺癌组织中,TOP2A蛋白与TOP2A基因的关系,17号染色体多体与HER2、TOP2A基因及蛋白的关系,和HER2、TOP2A和17号染色体多体三者和临床参数相关性。
方法：课题包括60例浸润性乳腺癌组织的石蜡包埋标本,其中IHC检测HER2蛋白表达(0/1+)(2+)(3+)分别占1/3。应用IHC检测这些患者的HER2和TOP2A蛋白表达状态,应用FISH检测这些患者的HER2和TOP2A基因表达状态及17号染色体状态。
结果：IHC检测HER2蛋白表达为(0/+)22人in the group of 22 HER2,其中FISH检测HER2基因非扩增21人,占95.5%(21/22),HER2基因扩增1人,占4.5%；IHC检测HER2蛋白表达为(3+)19人,其中FISH检测HER2基因扩增18人,占94.7%(18/19),HER2基因非扩增1人,占5.3%；分析IHC检测HER2蛋白(0/1+)组和(3+)和FISH检测HER2基因的结果。一致性较好(Kappa=0.902,P<0.05)17号染色体正常患者42人,HER2蛋白(3+)9人,占21.4%(9/42),HER(0/1+)和(2+),占78.6%(33/42)；17号染色体多体患者18人,HER2蛋白(3+)10人,占55.6%(10/18),HER(0/1+)和(2+)9人,占55.6%(9/18)。17号染色体多体组HER2(3+)比例多(x26.782,P=0.009)。17号染色体正常患者42人,HER2基因扩增20人,占47.6%(20/42),17号染色体多体患者18人,HER2基因扩增12人,占66.7%(12/18),17号染色体正常组和多体组HER2基因扩增患者百分比比较,结果应用卡方检验,差异无统计学意义(x2=1.837,P>0.05)。TOP2A蛋白表达阴性16例,其中TOP2A基因缺失1例,占6.3%(1/16)；TOP2A基因正常14例,占87.5(14/16)；TOP2A基因扩增1例,占6.3%(1/16)。TOP2A蛋白表达阳性44例,其中TOP2A基因缺失0例,TOP2基因阴性36例,占81.8(36/44)；TOP2A基因扩增8例,占18.2%(8/44)。TOP2A蛋白阴性表达和阳性表达两组的基因扩增情况比较,差异无统计学意义(x2=3.909,P=0.142,P>0.05)。17号染色体正常患者42人,TOP2A蛋白阳性表达29人,占69.0%(29/42),17号染色体多体患者18人,TOP2A蛋白阴性表达15人,占83.3%(15/18),17号染色体正常组和多体组TOP2A蛋白表达阳性率比较,结果差异无统计学意义(x2=1.315,P>0.05)。17号染色体正常患者42例,其中TOP2A基因缺失0例；TOP2A基因正常36例,占85.7(36/42)；TOP2A基因扩增6例,占14.3%(6/42)；17号染色体多体18例,其中TOP2A基因缺失1例,占5.6%(1/18),TOP2基因正常14例,占77.8(14/18)；TOP2A基因扩增3例,占16.7%(3/18)。17号染色体正常和多体时TOP2A基因扩增率的比较,差异无统计学意义(x2=2.476,P>0.05)。HER2基因扩增的32个患者中,TOP2A基因扩增7人,占21.9%(7/32),TOP2A基因缺失1人,占3.1%,HER2基因非扩增患者中TOP2A基因扩增2人,占7.1%。HER2基因扩增组与非扩增组的TOP2A基因扩增率比较,结果无统计学意义(P>0.05)。HER2基因扩增的32个患者中,TOP2A蛋白表达阳性27人,占84.4%(27/32),HER2基因非扩增患者中TOP2A蛋白表达阳性17人,占60.7%(17/28)。HER2基因扩增组与非扩增组的TOP2A蛋白阳性率比较,差异有统计学意义(x2=3.607,P=0.111,P>0.05)。HER2蛋白表达和基因扩增与淋巴结转移情况、ER、PR状态有关(P<0.05)；TOP2A蛋白阳性与PR状态有关(P<0.05)。
结论：1、对于IHC检测HER2蛋白(0/1+)和(3+)患者,IHC可以判定HER2状态,HER2蛋白(2+)必须行FISH检测来判定HER2基因状态。2、17号染色体多体与HER2蛋白过表达相关。3、TOP2A蛋白过表达,TOP2A基因异常和17号染色体多体之间不相关。4、HER2基因扩增的患者TOP2A蛋白阳性率高,提示HER2基因扩增患者应选择含蒽环类化疗药物的方案。
Purpose:To investigate the relationship between TOP2A protein expression and TOP2A gene abnormal,the relationship amang protein expression and genes of HER2 TOP2A and polysome 17, the relationship between HER2、TOP2A、polysome 17 and clinical parameters.
Methods:We analyzed paraffin sections from 60 patients with invasive dula cancer.IHC determined that 1/3 of the patients had HER2 protein expression (0/1+) (2+) (3+) respectively. IHC determined protein expression state of HER2 and TOP2A, while FISH ditermined HER 2 gene status、TOP2A gene status and chromosome 17 status.
Results:The score of (0/1+) in IHC identified 95.5%(21of 22cases)of the cases with HER2 non-amplification and 4.5%(1of 22 cases)of the cases with HER2 amplification; the score of (3+) in IHC identified 94.7%(18of 19cases)of the cases with HER2 amplification and 5.3%(lof 19 cases)of the cases with HER2 non-amplification.The concordance of IHC analysis for HER2 protein and FISH analysis for HER2 gene was well (Kappa=0.902, P< 0.05). Normal in chromosome 17 were detected in 42 patients:21.4%(9 of 42 cases) was HER2 protein (3+),78.6%(33 of 42 cases) was HER2 protein (0/1+)and(2+). polysomy 17 were detected in 18 patients:55.6%(9 of 42 cases) was HER2 protein (3+),78.6%(33 of 42 cases) was HER2 protein (0/1+)and(2+).HER2 protein (3+) was more in polysomy 17. Normal in chromosome 17 were detected in 42 patients:47.6%(20 of 42 cases) was HER2 gene amplifition, polysomy 17 were detected in 18 patients:66.7%(12 of 18 cases) was HER2 gene amplification. No statistically significant correlation was found between the two groups. TOP2A protein expression negative were detected in 16 patients:6.3%(1 of 16 cases) was TOP2A gene deletion,87.5%(14 of 16 cases) was TOP2A gene normal,6.3%(1 of 16 cases) was TOP2A gene amplification; TOP2A protein expression positive were detected in 44 patients:0 was TOP2A gene deletion,81.8%(36of 44 cases) was TOP2A gene normal,18.2%(8 of 44 cases) was TOP2A gene amplification; there was no statistically significant correlation between the TOP2A protein expression negative and positive. (x2= 3.909, P=0.142, P>0.05)。Normal in chromosome 17 were detected in 42 patients:69.0% (29 of 42 cases) was TOP2A protein expression positive;polysomy 17 were detected in 18 patients:83.3%(15 of 18 cases) was TOP2A protein expression negative. No statistically significant correlation was found between the two groups. (x 2= 1.315, P>0.05). Normal in chromosome 17 were detected in 42 patients:0 was TOP2A gene deletion,85.7%(36 of 42 cases) was TOP2A gene normal,14.3%(6 of 42 cases) was TOP2A gene amplification; polysomy 17 were detected in 18 patients:5.6% was TOP2A gene deletion,77.8%(14of 18 cases) was TOP2A gene normal,16.7%(3 of 18 cases) was TOP2A gene amplification; there was no statistically significant correlation between the chromosome 17 normal and polysome17. (x2=2.476, P>0.05).21.9% of the HER2 gene amplification samples were found in the group with TOP2A gene amplification,one case (3.1%) showed deletion of TOP2A gene.7.1% of the HER2 gene non-amplificantion samples were found in the group with TOP2A gene amplification, there was no statistically significant correlation between the chromosome 17 normal and polysomel7. (x2=2.476, P>0.05).84.4% of the HER2 gene amplification samples were found in the group with TOP2A protien positive,60.7% of the HER2 gene non-amplificantion samples were found in the group with TOP2A protien positive, there was statistically significant correlation between the chromosome 17 normal and polysome17. (x 2=2.476, P>0.05). HER2 protein and gene positive were faound to be associated with lympy node involvement and prog-esterone/estrogen receptor negativity. TOP2A protein positive were faound to be associated with prog-esterone receptor negativity.
Conclusion:1, For HER2 protein (0/1+) and (3+) by IHC, IHC can estimate HER2 protein state, for HER2 protein (2+), FISH must to estimate HER2 gene state.2, There was relation between ploysome 17 and HER2 protein expression.3, There was no relation among TOP2A protein expression TOP2A gene abnormal and ploysome 17.4, there was relation between HER2 gene amplification and TOP2A protein,promping HER2 gene amplification patients should choose anthracycline-based chemotherapy.
引文
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