17号染色体基因拷贝数对评价乳腺癌患者HER-2基因状况的影响

Effect of Chromosome 17 Copy Number on HER-2/neu Status Determination in Breast Cancers

目的探讨17号染色体的基因拷贝数对评价乳腺癌患者HER-2基因状况的影响。方法应用双色免疫荧光探针对294例免疫组化初筛的乳腺癌标本进行荧光原位杂交染色。采用HER-2基因拷贝数>4的绝对计数法及HER-2基因拷贝数比值法判定HER-2基因状况。结果当HER-2基因与17号染色体基因拷贝数比值>2时,45.24%(133/294)病例为阳性,绝对计数HER-2基因拷贝数>4时,阳性率为46.9%(138/294)。两者比较无统计学意义。但比值<2,绝对计数>4和比值>2,绝对计数<4的病例中,阳性率分别为3.77%和6.91%(P<0.05)。结论 FISH是比IHC更准确的方法。当17号染色体是异倍体时,导致17号基因拷贝数改变,降低了IHC检测的准确性。导致FISH绝对计数法在评价HER-2基因状况存在一定的偏差。而FISH比值法在17号染色体为异倍体时校正了17号染色体倍体的影响是最佳的评价方法 。

Objective To assess the effect of chromosome 17 copy number on HER-2/neu status determination in breast cancers.Method HER-2/neu gene copy and chromosome 17 centromere numbers were evaluated on 294 breast carcinomas using double color fluorescence in situ hybridization （FISH）.All of 294 have done by immunohistochemistry as a screening （0,1＋,2＋,3＋）.using a net HER-2/neu genecopy number 4 as a criterion.ratio as a alternative compared and related to immunohistochemistry done.Results When a ratio 2 was considered as criterion for FISH positivity,45.24% （133 of 294） of cases showed amplification versus 46.9% （138 of 294） by using a net HER-2/neu gene copy number 4 as a alternative criterion.3.77% （4 of 106） of cases having a ratio 2 had a net HER-2/neu gene copy number 4 and 6.91% （13 of 188） with a ratio 2 had a net HER-2/neu gene copy number.Conclusion A net increase in HER-2/neu gene copy number consecutive to polysomy 17 in the absence of specific gene amplification might lead to a strong protein overexpression in a small subset of breast carcinomas.17 copy number effect on HER-2/neu status determination.Determination by FISH is dependent on the ratio criterion considered for positivity in clinical practice.