肾上腺嗜酸细胞型皮质癌的临床病理特征及表皮生长因子受体基因状态

Clinicopathological Features and Epidermal Growth Factor Receptor Gene Status of Adrenocortical Oncocytic Carcinoma

目的探讨肾上腺嗜酸细胞型皮质癌临床病理特征及其表皮生长因子受体（epidermal growth factor receptor,EGFR）蛋白表达、基因突变和基因拷贝数改变情况。方法回顾性分析2000年1月至2009年12月在北京协和医院手术切除的9例肾上腺嗜酸细胞型皮质癌的临床特点、组织形态学特征,并以9例肾上腺嗜酸细胞型皮质腺瘤为对照,应用免疫组织化学、Scorpion ARMS突变系统及荧光原位杂交（fluorescence in situ hybridization,FISH）的方法分析EGFR在二者中的蛋白表达、基因突变和基因拷贝数改变的情况。结果 9例肾上腺嗜酸细胞型皮质癌中,Cushing综合征2例,无功能性皮质癌7例。病例随访时间6~56个月,皮质癌患者失访2例,死亡6例。肾上腺嗜酸细胞型皮质癌中EGFR蛋白过表达率为77.8%（7/9）,EGFR FISH阳性率为55.6%（5/9）;仅有22.2%（2/9）皮质腺瘤存在EGFR蛋白的表达,且EGFR FISH均为阴性。肾上腺嗜酸细胞型皮质腺瘤及皮质癌中均未检测出EGFR基因扩增及基因突变。结论肾上腺嗜酸细胞型皮质癌非常罕见,其诊断依据病理学及免疫表型,EGFR蛋白过表达和7号染色体的高多体性较腺瘤更常见,可能有助于与后者的鉴别诊断,也有可能成为今后临床分子靶向治疗的潜在方向。

Objective To explore the clinicopathological features of adrenocortical oncocytic carcinoma and protein expression , gene mutation , and gene copy number alteration of epidermal growth factor receptor （ EGFR） in this carcinoma .Methods We reviewed the clinical and histomorphological features of 9 adrenocorti-cal oncocytic carcinoma cases who received surgical resection in the period of January 2000 to December 2009 in Peking Union Medical College Hospital , and 9 adenoma cases were included as control .EGFR protein expres-sion , EGFR gene mutation and EGFR gene copy number alteration in both groups were detected by immunohisto -chemistry , Scorpion Amplification Refractory Mutation System （ ARMS ） , and fluorescence in situ hybridization （ FISH） , respectively . Results The 9 cases of adrenocortical oncocytic carcinomas included 2 cases of Cushing＇s syndrome and 7 cases of nonfunctional cortical carcinoma .All cases were followed up for 6 to 56 months, and 2 patients with adrenocortical oncocytic carcinomas lost to follow -up, and 6 died.In the adrenocorti-cal oncocytic carcinoma patients , EGFR overexpression was found in 77.8%（7/9）, and EGFR FISH was posi-tive in 55.6%（5/9）.In contrast, only 22.2% （2/9） of the adrenocortical adenoma patients showed EGFR weak expression and none had positive FISH result .No EGFR gene amplification or mutation was found in the 2 groups of patients .Conclusions Adrenocortical oncocytic carcinoma is rare .EGFR overexpression and chromo-some 7 polysomy are frequent abnormality in the adrenocortical oncocytic carcinomas , which may be used in the differential diagnosis .Also, an investigation of the gene status of EGFR should facilitate the identification of a target therapeutic regimen for carcinoma patients .