p16 FISH Deletion in Surface Epithelial Mesothelial Proliferations Is Predictive of Underlying Invasive Mesothelioma
p16 FISH Deletion in Surface Epithelial Mesothelial Proliferations Is Predictive of Underlying Invasive Mesothelioma
复制标题
DOI：
10.1097/pas.0000000000000176
复制
发表时间：
2014-05-01
影响因子：
5.6
通讯作者：
Churg, Andrew
中科院分区：
文献类型：
--
作者：
Hwang, Harry;Tse, Christopher;Churg, Andrew
沿着胸膜或腹膜表面的非典型间皮增生，没有侵袭性肿瘤的证据，这对诊断提出了挑战。荧光原位杂交（FISH）检测p16（CDKN 2A）纯合性缺失已被证明是间皮瘤增生恶性肿瘤的良好标志，但非典型表面增生与潜在间皮瘤之间p16状态的相关性尚未得到描述。我们使用p16 FISH研究了11例胸膜间皮瘤和7例腹膜间皮瘤，这些间皮瘤同时具有侵袭性成分和单独的表面间皮瘤增殖。在5/11例胸膜样本和1/7例腹膜样本中，侵袭性间皮瘤显示p16纯合缺失（所有病例中超过90%的细胞缺失）;在侵袭性肿瘤中缺失的所有6例病例中，表面增殖也是p16缺失。相反，12例浸润区未显示p16缺失的肿瘤表面成分也未缺失。我们的结论是：（1）浸润性间皮瘤附近的表面间皮瘤增殖显示与潜在肿瘤相同的p16 FISH模式，可能代表原位疾病或潜在间皮瘤沿着浆膜表面生长;（2）间皮瘤表面增生中的p16缺失与潜在间皮瘤中的p16缺失密切相关，并且由p16缺失的纯表面间皮瘤增殖组成的活检允许诊断间皮瘤而无需额外的活检，（胸腔镜/腹腔镜）或放射学证据弥漫性胸膜或腹膜肿瘤;（3）然而，在表面增殖中缺乏p16缺失并不能排除潜在的浸润性间皮瘤。
An atypical mesothelial proliferation along the pleural or peritoneal surface without evidence of invasive tumor poses a diagnostic challenge. Homozygous deletion of p16 (CDKN2A) by fluorescence in situ hybridization (FISH) has been shown to be a good marker of malignancy in mesothelial proliferations, but correlations of p16 status between atypical surface proliferations and underlying mesothelioma have not been described. We used p16 FISH to investigate 11 pleural and 7 peritoneal mesotheliomas that had both an invasive component and a separate surface mesothelial proliferation. In 5/11 pleural samples and 1/7 peritoneal samples, the invasive mesotheliomas showed homozygous deletion of p16 (all cases in excess of 90% of cells deleted); the surface proliferation in all 6 cases with deletion in the invasive tumor was also p16 deleted. Conversely, the 12 tumors that did not show p16 deletion in the invasive compartment also did not have deletion in the surface component. We conclude that (1) surface mesothelial proliferations near invasive mesotheliomas show the same pattern of p16 by FISH as the underlying tumor and may represent in situ disease or growth of the underlying mesothelioma along the serosal surface; (2) p16 deletion in mesothelial surface proliferations is strongly associated with p16 deletion in underlying mesotheliomas, and biopsies consisting of pure surface mesothelial proliferations that are p16 deleted allow a diagnosis of mesothelioma without an additional biopsy if there is clinical (thoracosopic/laparoscopic) or radiologic evidence of diffuse pleural or peritoneal tumor; (3) however, the absence of p16 deletion in surface proliferations does not rule out underlying invasive mesothelioma.