Fluorescence in situ hybridization in the definitive diagnosis of malignant mesothelioma in effusion cytology.
Fluorescence in situ hybridization in the definitive diagnosis of malignant mesothelioma in effusion cytology.
复制标题
荧光原位杂交在积液细胞学中明确诊断恶性间皮瘤。
作者：
S. Savic;N. Franco;B. Grilli;A. Barascud;M. Herzog;B. Bode;H. Loosli;P. Spieler;R. Schönegg;I. Zlobec;D. Clark;J. Herman;L. Bubendorf
背景
区分恶性间皮瘤 (MM) 和积液中的反应性间皮细胞 (RM) 非常困难。我们研究的目的是测试荧光原位杂交 (FISH) 检测到的染色体畸变在积液细胞学诊断 MM 中的作用，并探讨 p16、p14 和 p15 基因甲基化作为抑癌基因失活的替代机制的潜在作用。
方法
通过多靶点 FISH 检测对 52 例经活检证实的 MM 积液和 28 例良性积液进行回顾性分析，了解 3、7、17 和 9p21 染色体的畸变。如果结果为阴性，则分析相应的 MM 活检标本。对 FISH 阴性 MM 活检标本进行 p16、p14 和 p15 的甲基化特异性聚合酶链反应 (MSP)。
结果
经活检证实的 MM 积液中，79% 存在染色体畸变，最常见的发现是 9p21 缺失。所有良性积液的 FISH 均为阴性。 FISH 检测 MM 的敏感性、特异性以及阳性和阴性预测值分别为 79%、100%、100% 和 72%。经活检证实的 MM 的 9 例 FISH 阴性积液中，有 6 例的 MM 活检标本中也呈 FISH 阴性。与 12 份良性对照中的一份相比，五份 FISH 阴性活检标本中的四份显示 p16 和 p14 中启动子甲基化。
结论
FISH 是一种敏感且高度特异的积液细胞学明确诊断 MM 的方法。在 FISH 阴性 MM 亚型中，染色体区域 9p21 上的肿瘤抑制基因通常因启动子甲基化而失活。
BACKGROUND
Distinction of malignant mesothelioma (MM) from reactive mesothelial cells (RM) in effusions is notoriously difficult. The aim of our study was to test chromosomal aberrations detected by fluorescence in situ hybridization (FISH) in the diagnosis of MM in effusion cytology and to explore the potential role of p16, p14, and p15 gene methylation as an alternative mechanism of tumor suppressor gene inactivation.
METHODS
Fifty-two effusions of biopsy-proven MM and 28 benign effusions were retrospectively analyzed by multitarget FISH assay for aberrations of chromosomes 3, 7, 17, and 9p21. In case of a negative result, the corresponding MM biopsy specimen was analyzed. Methylation-specific polymerase chain reaction (MSP) for p16, p14, and p15 was performed on FISH-negative MM biopsy specimens.
RESULTS
Seventy-nine percent of effusions with biopsy-proven MM had chromosomal aberrations, with loss of 9p21 as the most common finding. All benign effusions were FISH negative. Sensitivity, specificity, and positive and negative predictive values for detection of MM by FISH were 79%, 100%, 100%, and 72%, respectively. Six of nine FISH-negative effusions with biopsy-proven MM were also FISH negative in the MM biopsy specimens. Four of five FISH-negative biopsy specimens showed promoter methylation in p16 and p14 as compared with one of 12 benign controls.
CONCLUSIONS
FISH is a sensitive and highly specific method for the definitive diagnosis of MM in effusion cytology. In the subset of FISH-negative MM, tumor suppressor genes on the chromosomal region 9p21 are often inactivated by promoter methylation.
DOI：
10.1073/pnas.93.18.9821
发表时间：
1996-09-03
影响因子：
11.1
作者：
Herman, JG;Graff, JR;Baylin, SB
通讯作者：
Baylin, SB