Interphase cytogenetic analysis in adrenal neoplasms

我们研究了43例原发性醛固酮增多症腺瘤和24例库欣综合征腺瘤的流式细胞术DNA含量和核分级。原发性醛固酮增多症腺瘤在流式细胞直方图上的4C峰明显宽于正常肾上腺或库欣综合征腺瘤（p<0.0001）。67例腺瘤中有30例呈二倍体，27例呈四倍体，8例呈非整倍体，17例正常肾上腺均呈二倍体。DNA倍性与临床综合征之间存在显著相关性，即原发性醛固酮增多症的腺瘤呈现四倍体DNA直方图的比例高于库欣综合征腺瘤（p=0.0004）。原发性醛固酮增多症腺瘤的核分级（III级和IV级）明显高于库欣综合征肿瘤（p=0.038）。在57例非整倍体肿瘤中，DNA倍性与核分级之间也存在显著的相关性，其中四倍体肿瘤多，核分级最高（p=0.042）。我们的研究结果表明，原发性醛固酮增多症相关的肾上腺皮质腺瘤经常表现出严重的核多形性，表明核多形性可能是由四倍体茎系引起的。对12例肾上腺皮质腺瘤（库欣综合征5例，原发性醛固酮增多症7例）的3、7、8、11、12、17号染色体进行了流式细胞术和间期荧光原位杂交（FISH）分析。DNA倍体分析显示8例二倍体和4例四倍体肿瘤，未发现DNA非整倍体。四倍体仅在原发性醛固酮增多症的腺瘤中发现，另一方面，FISH分析显示染色体畸变与DNA倍体之间存在一些差异。原发醛固酮增多症的腺瘤，不论其DNA倍性如何，均表现为两条或更多染色体的四体。与原发性醛固酮增多症的肿瘤相比，腺瘤伴Gushing综合征的染色体异常较少。然而，患有库欣综合征的5例AGAs中有3例具有8号染色体三体，此外，原发性醛固酮增多症的腺瘤经常表现为同一染色体三体。这些发现提示原发性醛固酮增多症的腺瘤通常具有异常的（四染色体）茎系，并且8号染色体三体可能在肾上腺皮质腺瘤的发展中起重要作用。少

We investigated the flow cytometric DNA content and nuclear grade in 43 adenomas associated with primary aldosteronism and 24 adenomas with Cushing's syndrome. Adenomas with primary aldosteronism had a significantly wider 4C peak on flow cytometric histogram than normal adrenal glands or adenomas with Cushing's syndrome (p<0.0001, respectively). Flow cytometric analysis showed diploidy in 30, tetraploidy in 27 and aneuploidy in 8 of the 67 adenomas, and all 17 normal adrenal glands showed diploidy. A significant correlation was noted between DNA ploidy and clinical syndrome, i.e., a larger proportion of adenomas with primary aldosteronism showed a tetraploid DNA histogram compared with adenomas with Cushing's syndrome (p=0.0004). Adenomas with primary aldosteronism had a significantly higher nuclear grade (III and IV) than did tumors with Cushing's syndrome (p=0.038). A significant correlation was also observed between DNA ploidy and nuclear grade in 57 nonaneuploid tumors, with tetrap … More loid tumors often showing the highest nuclear grade (p=0.042). Our results showed that adrenal cortical adenomas associated with primary aldosteronism often revealed severe nuclear pleomorphism, indicating that nuclear pleomorphism might be due to a tetraploid stemline.DNA ploidy by flow cytometry and interphase fluorescence in situ hybridization (FISH) analysis of chromosome 3, 7, 8, 11, 12, and 17 were performed on 12 adrenal cortical adenomas (5 with Cushing's syndrome and 7 with primary aldosteronism). DNA ploidy analysis revealed 8 diploid and 4 tetraploid tumors, and DNA aneuploidy was not found in this study. Tetraploidy was found only in adenomas with primary aldosteronism, On the other hand, FISH analysis revealed some discrepancies between the chromosomal aberrations and DNA ploidy. Adenomas with primary aldosteronism showed tetrasomy in two or more chromosomes analyzed, irrespective of heir DNA ploidy. Adenomas with Gushing' s syndrome had fewer chromosomal abnormalities compared with tumors with primary aldosteronism. However, three of five AGAs with Cushing's syndrome had trisomy of chromosome 8, and in addition, adenomas with primary aldosteronism frequently showed trisomy of the same chromosome. These findings suggest that adenomas with primary aldosteronism may often have an aberrant (tetrasomic) stemline, and that trisomy of chromosome 8 may play an important role in the development of adrenal cortical adenoma. Less