Institute for Pathology, University Hospital Basel, Schönbeinstrasse 40, 4031 Basel, Switzerland.
Chest. 2010 Jul;138(1):137-44. doi: 10.1378/chest.09-1951. Epub 2010 Feb 5.
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.
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.
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.
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.
在胸腔积液中区分恶性间皮瘤（MM）和反应性间皮细胞（RM）非常困难。我们研究的目的是检测荧光原位杂交（FISH）检测到的染色体异常在胸腔积液细胞学诊断 MM 中的作用，并探讨 p16、p14 和 p15 基因甲基化作为肿瘤抑制基因失活的替代机制的潜在作用。
回顾性分析 52 例经活检证实的 MM 和 28 例良性胸腔积液的多靶点 FISH 检测，以检测染色体 3、7、17 和 9p21 的异常。如果结果为阴性，则分析相应的 MM 活检标本。对 FISH 阴性的 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）。
79%的 MM 胸腔积液存在染色体异常，最常见的发现是 9p21 缺失。所有良性胸腔积液均为 FISH 阴性。FISH 检测 MM 的敏感性、特异性、阳性和阴性预测值分别为 79%、100%、100%和 72%。9 例 FISH 阴性 MM 胸腔积液中，有 6 例在 MM 活检标本中也是 FISH 阴性。5 例 FISH 阴性活检标本中，p16 和 p14 的启动子均有甲基化，而 12 例良性对照中只有 1 例有甲基化。
FISH 是胸腔积液细胞学中明确诊断 MM 的一种敏感且高度特异的方法。在 FISH 阴性 MM 的亚组中，染色体 9p21 上的肿瘤抑制基因通常因启动子甲基化而失活。
