Blanes Alfredo, Diaz-Cano Salvador J
Department of Pathology, University Hospital of Malaga, 29010 Malaga, Spain.
Hum Pathol. 2006 Oct;37(10):1295-303. doi: 10.1016/j.humpath.2006.04.025. Epub 2006 Jul 18.
Monoclonal adrenocortical lesions show inverse correlation between proliferation and apoptosis, with proliferation being the single most important criterion of malignancy in adrenal lesions. No study yet has evaluated the variability of proliferation regarding the clonal pattern and diagnosis in adrenocortical nodular hyperplasias (ACNHs), adrenocortical adenomas (ACAs), and adrenocortical carcinomas (ACCs). We studied 69 ACNHs, 64 ACAs, and 23 ACCs (World Health Organization criteria) from 156 females. Clonality HUMARA test (from microdissected DNA samples), DNA content and proliferation analysis (slide and flow cytometry), and mitotic figure (MF) counting/50 high-power fields (HPFs) were performed in the same areas. Heterogeneity was assessed by 5cER (percentage of nonoctaploid cells with DNA content exceeding 5c) and standard deviation of MF/HPF. Statistics included analysis of variance/Student t tests regarding the clonal patterns and diagnosis. Polyclonal patterns were observed in 48 of 62 informative ACNHs and 7 of 56 informative ACAs, and monoclonal in 14 of 62 ACNHs, 49 of 56 ACAs, and 21 of 21 ACCs, with all hyperdiploid lesions (14 ACCs and 13 ACAs) being monoclonal. The standard deviation of MF/HPF progressively increased in ACNH-ACA-ACC (0.048 +/- 0.076, 0.110 +/- 0.097, 0.506 +/- 0.291, respectively; P = .0023), but did not differentiate ACNH/ACA. Only tetraploid percentage (P = .0496) and 5cER (P = .0352) distinguished polyclonal (3.64 +/- 2.20 and 0.14 +/- 0.15) from monoclonal (7.25 +/- 7.52 and 1.00 +/- 1.74) benign lesions. Malignancy significantly correlated with a low diploid percentage and high tetraploid percentage. Cell kinetic heterogeneity is the hallmark of adrenocortical neoplasms: tetraploid/hypertetraploid cell accumulation characterizes monoclonal lesions (suggesting nondisjunctional mitoses), whereas heterogeneously distributed mitotic figures and decreased diploid percentage define ACCs.
单克隆肾上腺皮质病变显示增殖与凋亡呈负相关，增殖是肾上腺病变恶性程度的唯一最重要标准。尚无研究评估肾上腺皮质结节性增生（ACNH）、肾上腺皮质腺瘤（ACA）和肾上腺皮质癌（ACC）中增殖在克隆模式和诊断方面的变异性。我们研究了156名女性的69例ACNH、64例ACA和23例ACC（依据世界卫生组织标准）。在相同区域进行克隆性HUMARA检测（来自显微切割的DNA样本）、DNA含量及增殖分析（玻片和流式细胞术）以及有丝分裂象（MF）计数/50个高倍视野（HPF）。通过5cER（DNA含量超过5c的非八倍体细胞百分比）和MF/HPF的标准差评估异质性。统计学分析包括针对克隆模式和诊断的方差分析/学生t检验。在62例信息充分的ACNH中的48例和56例信息充分的ACA中的7例观察到多克隆模式，在62例ACNH中的14例、56例ACA中的49例和21例ACC中的21例观察到单克隆模式，所有超二倍体病变（14例ACC和13例ACA）均为单克隆。MF/HPF的标准差在ACNH - ACA - ACC中逐渐增加（分别为0.048±0.076、0.110±0.097、0.506±0.291；P = 0.0023），但无法区分ACNH/ACA。只有四倍体百分比（P = 0.0496）和5cER（P = 0.0352）能够区分多克隆（3.64±2.20和0.14±0.15）与单克隆（7.25±7.52和1.00±1.74）良性病变。恶性程度与低二倍体百分比和高三倍体百分比显著相关。细胞动力学异质性是肾上腺皮质肿瘤的标志：四倍体/超四倍体细胞积累是单克隆病变的特征（提示有丝分裂不分离），而异质性分布的有丝分裂象和降低的二倍体百分比则界定了ACC。
