胃癌中HER-2表达异质性的病理学分析

Heterogeneity of HER-2 expression in gastric cancer: a pathological analysis

目的检测胃癌组织中HER-2蛋白表达水平和基因扩增情况,定量分析HER-2表达和分布特征的异质性,探讨其在判读中的影响。方法应用免疫组化检测并观察胃癌组织中HER-2蛋白表达水平及分布特征,应用荧光原位杂交(fluorescence in situ hybridization,FISH)技术检测HER-2基因扩增情况,并运用欧式距离等进行统计学处理。结果 373例胃癌手术切除标本中HER-2蛋白阳性率(3+)为12.33%,与基因扩增情况显著相关(P<0.001)。98例有HER-2蛋白表达的标本总异质性、组内异质性及组间异质性大小差异均有统计学意义(P值分别为0.025、0.001、0.040);组内异质性大小明显低于组间异质性。根据标准判读为HER-2蛋白为2+及3+的病例异质性最大,1+病例最小。HER-2蛋白表达分布较均一的病例近乎为零,而同时具有阴阳脸及花斑样特征的病例最多。根据标准判读HER-2蛋白为0的病例中,有7例具有明显异质性。结论胃癌组织中HER-2蛋白表达的异质性较大且类型多样,判读时首先要增加观察视野,选择至少2个组织块进行HER-2蛋白检测;其次无论HER-2蛋白表达水平高低,均需同时检测基因扩增情况,以确保判读结果的准确性,更好的指导临床用药。

Purpose To detect HER-2 protein status and gene amplification in the gastric carcinoma, to quantitatively study the heter- ogeneity of HER-2 status and distribution characteristics, and to discuss influence of it on the interpretation. Methods The HER-2 protein status and distribution characteristics were evaluated using immunohistoehemistry, while its gene amplification was detected by fluorescence in situ hybridization （FISH） technology. And statistical processing was used such as the variance analysis. Results Positive expression of HER-2 protein （3 ＋ ） was found in 46 （ 12. 33% , 46/373 ） surgical removal specimens of gastric carcinoma, and there was the significant correlation compared with its gene amplification （P 〈 0. 001 ）. In 98 samples of HER-2 protein staining, there was statistical significance about the total, intra-group and inter-group heterogeneity （ P values were 0.025, 0. 001,0. 040, respectively）, and the size of it in the intra-group was lower than that in the inter-group. That heterogeneity about the level of 2 ＋ and 3 ＋ was the maximum in all cases according to the criteria, while the 1 ＋ was the minimum. It was the most cases that had the characteristics of both negative or positive reaction in different portion of the tissue and spotted samples, while there was almost no case with even distribution in HER-2 expression. There was also obvious heterogeneity in seven negative cases according to the standards. Conclusion It is necessary for us to select at least two of the tissue blocks and to increase the view fields when evaluation of HER-2 status in gastric cancer because of its obvious heterogeneity and uneven distribution characteristics. Meanwhile, HER-2/neu gene amplification result must be used in combination with the protein expression level to ensure the accuracy of interpretation and better guiding drug use.