肾上腺皮质癌、腺瘤临床病理特征分析和表皮生长因子受体、血管内皮生长因子的表达及意义

Clinicopathologic features and expression of epidermal growth factor receptor and vascular endothelial growth factor in adrenocortical tumors

目的探讨肾上腺皮质癌、腺瘤临床病理特征及表皮生长因子受体（EGFR）、血管内皮生长因子（VEGF）的表达及意义。方法选取2001年7月至2010年7月在北京协和医院经手术治疗且具有完整的临床、病理资料的肾上腺皮质肿瘤存档石蜡标本42例，其中肾上腺皮质腺瘤（ACC）、肾上腺皮质癌（ACA）各21例，对临床资料进行回顾性分析，采用WEISS系统评分，免疫组织化学检测二者EGFR和VEGF的表达情况，并进行随访。结果（1）临床特点：9例表现为原发性醛固酮综合征，其中8例良性，1例恶性。ACC肿瘤平均直径11．7cm，病程8．5个月，ACA肿瘤平均直径3．0cm，病程为45．6个月。（2）病理特点：ACA患者WEISS得分全部≤2分，平均0．9分；ACC患者得分〉4分，平均6．6分。窦隙浸润与转移有一定相关性（P〈0．01）。（3）免疫组织化学：ACC中，EGFR阳性率61．9％（13／21），而ACA中除5例呈1＋、1例呈2＋外，其余均为阴性，两者表达差异有统计学意义（P=0．030）。ACC中，VEGF阳性率为71．4％（15／21），其中3＋占28．6％（6／21）；2＋占28．6％（6／21）；ACA中，只有3例呈2＋，4例呈1＋，其余全部为阴性，两者表达差异有统计学意义（P=0．013）。且VEGF强阳性（3＋）与静脉浸润相关（P=0．028）。（4）生存分析：随访到的16例ACC患者，其肿瘤的质量与预后有一定的相关性（P=0．468）。结论肿瘤的大小、质量、内分泌特征在提示良恶性方面有重要意义。WEISS得分≥3分诊断肾上腺皮质癌效能很高，且窦隙状结构浸润与转移关系密切。EGFR、VEGF表达对肾上腺皮质癌和腺瘤有重要鉴别诊断价值。

Objective To study the clinicopathologic features and expression of epidermal growth factor receptor （EGFR） and vascular endothelial growth factor （VEGF） in adrenocortical tumors. Methods Forty-two cases of adrenocortical tumors operated at the Beijing Union Medical College Hospital during the period from July, 2001 to July, 2010 were retrospectively reviewed. Immunohistochemical study for EGFR and VEGF was carried out. The clinical information and follow-up data were analyzed. Results The cases included 21 adrenocortical carcinomas （ACC） and 21 adrenocortical adenomas （ACA）. Nine patients suffered from primary aldosterone syndrome, including 8 cases with ACA and 1 case with ACC. The average tumor size, tumor weight, and duration between disease onset and diagnosis in the 21 cases of ACC were 11.7 era, 542 g and 8.5 months, respectively. This was in contrast to 3 cm, 9. 8 g and 45.6 months, respectively in cases of ACA. Histologically, the WEISS score in all the 21 cases of ACA was ~〈2 （average = 0. 9 ）. None of the ACC cases had score less than 4 （ average = 6. 6 ）. The presence of sinus invasion correlated with tumor metastasis （ P 〈 0.01 ）. Immunohistochemical study showed that EGFR was expressed in 61.9% of ACC patients （ 13/21 ）, whereas EGFR staining was mostly negative in ACA （ except for weakstaining in 5 cases and moderate staining in 1 case）. The difference of EGFR expression between ACC and ACA was statistically significant （P = 0. 030）. On the other hand, the positive rate of VEGF in ACC was 71.4% （15/21）, including 28.6% （6/21） with strong expression and 28.6% （6/21） with moderate expression. In contrast, the expression rate of VEGF in ACA was 30.0% （7/21）, including 14. 3% （3/21） with moderate expression. The difference of VEGF expression between ACC and ACA was statistically significant （P--0. 013 ）. There was correlation between VEGF expression and venous invasion （P = O. 028 ）. The average duration of survival in patients with ACC was shorter than that in ACA. The tumor weight in ACC also correlated with prognosis. Conclusions Tumor size, weight and presence of endocrine symptoms may help in the differential diagnosis between ACC and ACA. A WEISS score of 〉1 3 highly suggests ACC. The presence of sinus invasion is associated with metastasis. EGFR or VEGF expression may also be important in differentiating ACC from ACA.