涎腺癌组织中EGFR和HER-2表达及临床意义

Expression of EGFR and HER-2 and their clinical significancein salivary gland carcinoma

目的探讨黏液表皮样癌、腺样囊性癌和腺泡细胞癌中EGFR和HER-2基因/蛋白表达及临床意义。方法采用免疫组化EnVision两步法检测80例涎腺癌(黏液表皮样癌30例、腺样囊性癌30例、腺泡细胞癌20例)和30例良性多形性腺瘤中EGFR和HER-2蛋白表达;采用荧光原位杂交技术检测涎腺癌中EGFR和HER-2基因扩增。结果 (1)涎腺癌中EGFR和HER-2蛋白阳性率分别为71.25%和32.5%,高于良性多形性腺瘤组(P均<0.05),其中以黏液表皮样癌中EGFR和HER-2蛋白阳性率最高,EGFR蛋白的表达强度最高(P均<0.05)。(2)EGFR和HER-2蛋白表达与涎腺癌患者性别、年龄、肿瘤最大直径、肿瘤分化程度、组织学亚型无关(P均>0.05);涎腺癌中EGFR和HER-2蛋白表达无相关性(rs=0.166,P>0.05)。(3)涎腺癌中EGFR基因高多体扩增的总阳性率为18.75%(15/80),其中黏液表皮样癌13例,腺样囊性癌2例,阳性率分别为43.3%和6.7%,相应蛋白表达强度均为()或(),表达强度和基因扩增之间呈明显正相关(rs=0.491,P<0.01);涎腺癌中未检测到HER-2基因扩增及17号染色体多体。(4)EGFR蛋白(/)组和基因扩增组患者的生存时间比蛋白(-/+)组和无基因扩增组均明显缩短(P均<0.05)。结论黏液表皮样癌高频率、高强度表达EGFR,并发生高多体基因扩增,可作为其分子靶向治疗的靶点。黏液表皮样癌、腺样囊性癌和腺泡细胞癌中HER-2蛋白弱表达,未检测到基因扩增。

Purpose To evaluate the differences and clinical significances of the expression of EGFR and HER-2 in mucoepidermoid carcinoma, adenoid cystic carcinoma and acinar cell carcinoma. Methods The expression of EGFR and HER-2 proteins in 80 cases of salivary gland carcinoma （ including 30 mucoepidermoid carcinomas, 30 adenoid cystic carcinomas and 20 acinar cell carcinomas） and 30 cases with pleomorphie adenoma was detected by immunohistochemical method, and the gene amplifications of EGFR and HER- 2 in salivary gland carcinoma were detected by fluorescence in situ hybridization. Results The expression rates of EGFR and HER-2 proteins in salivary gland carcinoma were 71.25% and 32. 5% respectively, which were both higher than those in pleomorphic adenoma （ P 〈 0. 05 ）. The expression rates of EGFR and HER-2 proteins and intensity of EGFR protein in mucoepidermoid carcinoma were the highest （ P 〈 0. 05 ）. There were no signiflcances among different gene, age, maximum diameter, tumor differentiation and tissue subtypes （P 〉0.05）. There was no significant correlation between the expression of EGFR and HER-2 proteins （r = 0. 166, P 〉 0. 05 ）. High polysomy amplification of EGFR gene was detected in 15 of 80 cases of salivary gland carcinomas （ 18. 75% ）, including 13 cases of mucoepidermoid carcinoma （43.3%） and 2 cases of adenoid cyst carcinoma （6.7%） , but HER-2 gene amplification and 17 chromosome polysomy were not detected. EGFR protein intensity in the gene amplification cases were moderately or strongly positive. The positive correlation was showed between EGFR protein intensity and gene amplification （rs = 0. 491, P 〈 0. 01 ）. Compared with EGFR negative/low expression and negative amplification groups, the survival time was significantly shortened in EGFR moderate/ strong expression and gene amplification groups （ P 〈 0.05 ）. Conclusions EGFR protein overexpression and its high polysomy amplification in mueoepidermoid carcinoma can be regarded as a target for molecular targeted therapy. HER-2 may not be a suitable target because of its low protein expression and negative gene amplification in mucoepidermoid carcinoma, adenoid cystic carcinoma and acinar cell carcinoma.