Department of Otorhinolaryngology and Maxillofacial Surgery, Zealand University Hospital, Køge, Denmark.
Department of Otorhinolaryngology Head and Neck Surgery and Audiology, Rigshospitalet, Copenhagen, Denmark.
Acta Ophthalmol. 2018 Nov;96(7):e768-e771. doi: 10.1111/aos.13667. Epub 2018 Feb 13.
Lacrimal gland tumours constitute a wide spectrum of neoplastic lesions that are histologically similar to tumours of the salivary gland. In the salivary gland, pleomorphic adenoma (PA) is frequently characterized by recurrent chromosomal rearrangements of the PLAG1 and HMGA2 genes, a genetic feature retained in carcinoma ex pleomorphic adenoma (ca-ex-PA) that makes it possible to distinguish ca-ex-PA from de novo carcinomas. However, whether PLAG1 and HMGA2 gene rearrangements are found in lacrimal gland PA and ca-ex-PA is not known.
Twenty-one lacrimal gland PAs and four ca-ex-PAs were retrospectively reviewed and subjected to break-apart fluorescence in situ hybridization (FISH) for rearrangements of the PLAG1 gene. Cases without PLAG1 abnormalities were subjected to HMGA2 break-apart FISH. Immunohistochemical staining for PLAG1 and HMGA2 protein was performed and correlated with gene status.
Sixteen of 21 PAs showed rearrangement of PLAG1 and were all positive for PLAG1 protein. Two of the remaining five PAs showed rearrangement of HMGA2 and were the only cases positive for HMGA2 with immunohistochemistry. The three FISH-negative PAs expressed PLAG1 protein. All four ca-ex-PAs showed rearrangement of PLAG1 and expressed PLAG1 protein. None of the de novo carcinomas showed rearrangement of either of the two genes or expression of the two proteins.
Rearrangement of PLAG1 and HMGA2 and expression of the corresponding proteins are frequent and specific findings in lacrimal gland PA and ca-ex-PA. The mechanism for PLAG1 overexpression in FISH-negative PAs is yet to be clarified.
泪腺肿瘤是一组广泛的肿瘤病变，其组织学上与唾液腺肿瘤相似。在唾液腺中，多形性腺瘤（PA）常表现为 PLAG1 和 HMGA2 基因的反复染色体重排，这种遗传特征在癌旁多形性腺瘤（ca-ex-PA）中得以保留，使其能够与新发癌区分开来。然而，PLAG1 和 HMGA2 基因重排在泪腺 PA 和 ca-ex-PA 中是否存在尚不清楚。
回顾性分析 21 例泪腺 PA 和 4 例 ca-ex-PA，行 PLAG1 基因断裂分离荧光原位杂交（FISH）检测基因重排。无 PLAG1 异常的病例进行 HMGA2 断裂分离 FISH。行 PLAG1 和 HMGA2 蛋白免疫组织化学染色，并与基因状态相关联。
21 例 PA 中有 16 例显示 PLAG1 重排，均为 PLAG1 蛋白阳性。其余 5 例中有 2 例显示 HMGA2 重排，这是仅有的 2 例 HMGA2 免疫组织化学阳性病例。3 例 FISH 阴性的 PA 表达 PLAG1 蛋白。4 例 ca-ex-PA 均显示 PLAG1 重排并表达 PLAG1 蛋白。没有任何新发癌显示这两个基因的任何一个重排或两种蛋白的表达。
PLAG1 和 HMGA2 的重排以及相应蛋白的表达在泪腺 PA 和 ca-ex-PA 中是常见且特异的发现。在 FISH 阴性的 PA 中 PLAG1 过表达的机制尚待阐明。
