Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Histopathology. 2018 Jan;72(2):285-293. doi: 10.1111/his.13341. Epub 2017 Oct 19.
Pleomorphic adenoma gene 1 (PLAG1) gene rearrangement is the most common genetic abnormality in pleomorphic adenoma (PA), resulting in overexpression of PLAG1 protein. PA and carcinoma ex pleomorphic adenoma (CA ex-PA) can mimic various benign and malignant salivary gland tumours. The aims of this study are to evaluate the sensitivity and specificity of PLAG1 immunohistochemistry (IHC) in the differential diagnosis of PA and CA ex-PA and to compare the PLAG1 immunohistochemical results to PLAG1 gene abnormalities as detected by fluorescence in-situ hybridisation (FISH).
PLAG1 immunostaining was performed on 83 salivary gland tumours, including 23 PA, 15 CA ex-PA and 45 other salivary gland tumours. In addition, PLAG1 FISH was performed in 44 cases for the presence of gene rearrangements/amplifications. The results showed high sensitivity of PLAG1 IHC in 96% of PA; however, discordant results between PLAG1 FISH abnormalities and IHC were noted in 15 of 44 cases (34%). Seven PA, four de-novo myoepithelial carcinomas and one basal cell adenocarcinoma had negative FISH results, but were positive for IHC; while three salivary duct carcinomas (SDC) ex-PA were positive for FISH but negative for IHC. PLAG1 IHC can differentiate CA ex-PA from de-novo SDC (P = 0.02), but not from de-novo myoepithelial carcinoma. PLAG1 IHC is a sensitive marker for PA. This could be due to PLAG1 gene abnormalities beyond FISH resolution.
A negative PLAG1 IHC might be helpful in excluding a PA diagnosis. Interestingly, in the context of CA ex-PA, FISH is more sensitive than IHC in detecting PLAG1 abnormalities.
多形性腺瘤基因 1（PLAG1）基因重排是多形性腺瘤（PA）中最常见的遗传异常，导致 PLAG1 蛋白过表达。PA 和癌旁多形性腺瘤（CA ex-PA）可模拟各种良性和恶性涎腺肿瘤。本研究旨在评估 PLAG1 免疫组化（IHC）在 PA 和 CA ex-PA 鉴别诊断中的敏感性和特异性，并将 PLAG1 免疫组化结果与荧光原位杂交（FISH）检测到的 PLAG1 基因异常进行比较。
对 83 例涎腺肿瘤进行了 PLAG1 免疫组化染色，包括 23 例 PA、15 例 CA ex-PA 和 45 例其他涎腺肿瘤。此外，对 44 例进行了 PLAG1 FISH 以检测基因重排/扩增。结果显示，PA 中 PLAG1 IHC 的敏感性高达 96%；然而，在 44 例中有 15 例（34%）出现 PLAG1 FISH 异常与 IHC 结果不一致。7 例 PA、4 例原发性肌上皮癌和 1 例基底细胞腺癌 FISH 结果阴性，但 IHC 阳性；而 3 例 CA ex-PA 则 FISH 阳性而 IHC 阴性。PLAG1 IHC 可将 CA ex-PA 与原发性涎腺癌（SDC）区分开（P=0.02），但不能与原发性肌上皮癌区分开。PLAG1 IHC 是 PA 的敏感标志物。这可能是由于 PLAG1 基因异常超出了 FISH 的分辨率。
PLAG1 IHC 阴性可能有助于排除 PA 诊断。有趣的是，在 CA ex-PA 中，FISH 在检测 PLAG1 异常方面比 IHC 更敏感。
