Wachenfeld C, Beuschlein F, Zwermann O, Mora P, Fassnacht M, Allolio B, Reincke M
Schwerpunkt Endokrinologie, Medizinische Universitätsklinik Würzburg, Würzburg, Germany.
Eur J Endocrinol. 2001 Sep;145(3):335-41. doi: 10.1530/eje.0.1450335.
Adrenocortical carcinoma (ACC) is a rare neoplasm with poor prognosis. Discerning ACCs from benign adenomas histologically may be difficult if invasion into surrounding tissues or metastases are missing.
In order to establish molecular markers for malignancy, we analyzed seven normal adrenals, three massive macronodular ACTH-independent adrenocortical hyperplasias (MMAHs), 30 adrenocortical adenomas (ACAs) and ten ACCs.
All tissues were studied for the presence of alterations in the p53 tumor suppressor gene using the PAb 1801 antibody, which detects mutant p53 protein and the pYNZ22 microsatellite marker to show loss of heterozygosity (LOH) at 17p, for expression of the proliferation-associated antigen Ki67 using the MIB1 antibody, for the rate of apoptotic tumor cells with the TdT-mediated dUTP biotin nick end labeling (TUNEL) method, and for LOH of 11q13 (menin gene locus) with the D11S956 microsatellite marker.
0/3 MMAH, 1/28 ACA and 3/10 ACC revealed immunopositive staining for p53. LOH for pYNZ22 was observed in 1/3 MMAH, 1/23 informative ACA and 6/6 informative ACC. The rate of apoptotic cells was significantly higher in ACC (P<0.0001 by ANOVA) than in ACA but there was some overlap between groups. The Ki67 index (% immunopositive cells) was 1.9+/-1.30% (mean+/-s.d.) in normal adrenals, 3.47+/-1.37% in MMAH, and 2.11+/-1.01% in ACA. ACC had the highest Ki67 index of 11.94+/-7.58% distinguishing all ACC from the ACA and MMAH studied with a cut-off level of 5%. LOH for 11q13 was detected in 2/3 MMAH, 5/26 ACA and 6/8 ACC.
We conclude that a Ki67 index above 5% is a sensitive and specific indicator of ACC and may be useful in the differentiation of adenomas from carcinomas.
肾上腺皮质癌（ACC）是一种预后较差的罕见肿瘤。如果没有发现侵犯周围组织或转移，从组织学上鉴别ACC与良性腺瘤可能会很困难。
为了建立恶性肿瘤的分子标志物，我们分析了7个正常肾上腺、3个巨大的促肾上腺皮质激素非依赖性肾上腺皮质增生（MMAH）、30个肾上腺皮质腺瘤（ACA）和10个ACC。
使用检测突变型p53蛋白的PAb 1801抗体和显示17p杂合性缺失（LOH）的pYNZ22微卫星标志物研究所有组织中p53肿瘤抑制基因的改变情况，使用MIB1抗体检测增殖相关抗原Ki67的表达，用TdT介导的dUTP生物素缺口末端标记（TUNEL）法检测凋亡肿瘤细胞的比例，并用D11S956微卫星标志物检测11q13（menin基因位点）的LOH。
3个MMAH中0个、28个ACA中1个、10个ACC中3个显示p53免疫阳性染色。在1个MMAH、23个信息充分的ACA中的1个和6个信息充分的ACC中观察到pYNZ22的LOH。ACC中的凋亡细胞比例显著高于ACA（方差分析P<0.0001），但两组之间存在一定重叠。正常肾上腺的Ki67指数（免疫阳性细胞百分比）为1.9±1.30%（平均值±标准差），MMAH为3.47±1.37%，ACA为2.11±1.01%。ACC的Ki67指数最高，为11.94±7.58%，以5%为临界值可将所有ACC与所研究的ACA和MMAH区分开来。在2个MMAH、26个ACA中的5个和8个ACC中的6个中检测到11q13的LOH。
我们得出结论，Ki67指数高于5%是ACC的一个敏感且特异的指标，可能有助于腺瘤与癌的鉴别。
