Abati A, Sanjuan X, Wilder A, Linehan W M, Hewitt S M, Merino M J
Laboratory of Pathology, Cytopathology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1500, USA.
Cancer. 1999 Aug 25;87(4):231-7.
Loss of heterozygosity (LOH) for several tumor suppressor genes (including loci on 3p, 1p, and 17p,) has been documented in surgical specimens of adrenal cortical carcinomas (ACCA) without accompanying losses in benign hyperplastic and adenomatous adrenal cortical lesions (ACL). This disparate pattern of LOH raises the possibility of exploitation of these differences for diagnostic utilization. Cytologic differentiation of benign versus malignant ACL may be impossible based solely on fine-needle aspiration (FNA) material. The authors attempted to extrapolate the genetic findings on surgical specimens to FNA specimens of ACL to determine whether LOH studies could be utilized as a definitive diagnostic tool.
Microdissection of archival material was performed on FNAs of ten ACCAs (stained with the Papanicolaou and Diff-Quik stains) with corresponding histologic material (stained with hematoxylin and eosin), one FNA of a benign ACL, and three touch preparations of benign adrenal cortex. LOH analysis was performed by polymerase chain reaction (PCR) with flanking markers for the following putative tumor suppressor genes: p53 (17p13; TP53), 1p (1p36; D1S165), and the von Hippel-Lindau gene at 3p25 (D3S1038 and D3S1110).
Similar results were obtained with cytologic and histologic material. As expected, benign ACL showed no LOH for the markers examined. Of the informative ACCA cases, 70% showed LOH for at least 1 of the 3 markers tested on both FNA and histologic samples. For all cases with amplifiable DNA, there was a 100% concordance rate for LOH between cytologic and histologic material, with at least 7 of the 10 cytologic samples originating from metastatic lesions and all of the surgical material originating from the primary adrenal neoplasm.
The results of this study suggest that the combination of microdissection and PCR for LOH of p53, 1p, and 3p25 from FNA material has the potential to be utilized to distinguish ACCA from benign ACL in informative cases. It also shows a 100% concordance rate between metastatic and primary ACCAs for the losses observed, a finding that can be extremely useful for the definitive identification of metastatic lesions. Archival cytologic preparations of ACCA are a reliable source of DNA for LOH studies. [See editorial counterpoint on pages 173-5 and reply to counterpoint on pages 176-7, this issue.] Cancer (Cancer Cytopathol)
在肾上腺皮质癌（ACCA）手术标本中已记录到多个肿瘤抑制基因（包括3p、1p和17p位点）的杂合性缺失（LOH），而在良性增生性和腺瘤性肾上腺皮质病变（ACL）中未伴随缺失。这种不同的LOH模式增加了利用这些差异进行诊断的可能性。仅基于细针穿刺（FNA）材料可能无法实现良性与恶性ACL的细胞学鉴别。作者试图将手术标本的基因研究结果外推至ACL的FNA标本，以确定LOH研究是否可作为一种确定性诊断工具。
对10例ACCA的FNA（用巴氏染色和Diff - Quik染色）及相应的组织学材料（用苏木精和伊红染色）、1例良性ACL的FNA以及3例良性肾上腺皮质的印片进行存档材料的显微切割。通过聚合酶链反应（PCR）对以下假定的肿瘤抑制基因进行LOH分析，其侧翼标记为：p53（17p13；TP53）、1p（1p36；D1S165）以及3p25处的von Hippel - Lindau基因（D3S1038和D3S1110）。
细胞学和组织学材料获得了相似的结果。正如预期的那样，良性ACL在所检测的标记中未显示LOH。在信息充分的ACCA病例中，70%在FNA和组织学样本上对所检测的3个标记中的至少1个显示出LOH。对于所有可扩增DNA的病例，细胞学和组织学材料之间的LOH一致性率为100%，10个细胞学样本中至少7个来自转移灶，所有手术材料均来自原发性肾上腺肿瘤。
本研究结果表明，对FNA材料进行显微切割并对p53、1p和3p25进行LOH的PCR检测，有可能在信息充分的病例中用于区分ACCA与良性ACL。它还显示出转移型和原发性ACCA之间在所观察到的缺失方面一致性率为100%，这一发现对于明确识别转移灶可能极为有用。ACCA的存档细胞学标本是用于LOH研究的可靠DNA来源。[见本期第173 - 175页的编辑观点及第176 - 177页对观点的回应。]癌症（癌症细胞病理学）
