Multiple fusion variants of PLAG1 and HMGA2 have been reported; currently, however, little is known regarding the clinicopathological impacts of these fusion types METHODS AND RESULTS: We examined the PLAG1- and HMGA2-related fusion status in 105 PAs and 11 cases of carcinoma ex PAs (CXPA) arising from salivary glands and lacrimal glands to elucidate their correlation to the clinicopathological factors.
Taken together, these results indicated that lncRNAs and mRNAs were differentially expressed in PA tissues obtained from PLAG1 transgenic mice as compared with those from control mice.
However, numerous molecular/genetic advances in the understanding of salivary gland neoplasms during the last decade have facilitated the development of many useful diagnostic markers, such as PLAG1 and HMGA2 immunohistochemistry for pleomorphic adenoma and ETV6 fluorescence in situ hybridization for secretory carcinoma.
On the basis of combined morphologic and molecular evidence of PA, 4 subsets of SDC emerged: 1) carcinomas with morphologic evidence of PA but intact PLAG1 and HMGA2 (n = 22); 2) carcinomas with PLAG1 alteration (n = 18) or 3) HMGA2 alteration (n = 12); and 4) de novo carcinomas, without morphologic or molecular evidence of PA (n = 14).
Morphological findings displayed typical features of PA. Immunohistochemical staining showed that tumor cells of both primary and metastasizing lesions were positive for pleomorphic adenoma gene (PLAG) 1, which is a sensitive marker for PA. Gene fusions involving PLAG1 were examined by reverse transcription-polymerase chain reaction.
As PLAG1 and HMGA2 rearrangements are the most common genetic events in pleomorphic adenomas, we sought to investigate if these abnormalities are also present in the skin/soft tissue ME lesions.
Our results suggest that soft tissue myoepithelioma may be a pathogenetically distinct tumor entity from pleomorphic adenoma based on the absence of PLAG1 overexpression and characteristic fusion genes.
From a large body of research, it has been well established that rearrangement of pleomorphic adenoma gene 1 (PLAG1) leads to aberrant expression of its protein and is pathogenically relevant in the development of salivary mixed tumors.
The present results also suggest that overexpression of PLAG1 is essential for the tumorigenesis of pleomorphic adenomas, although the mechanisms mediating PLAG1 overexpression seem to be variable.
To evaluate a possible genetic relationship between these soft tissue and salivary gland tumors, PLAG1 expression levels and the genomic status of PLAG1 and HMGA2 were investigated in five soft tissue myoepitheliomas and one pleomorphic adenoma.
The PLAG1 proto-oncogene was discovered by studying the t(3;8)(p21;q12) chromosome translocation, which frequently occurs in human pleomorphic adenomas of the salivary glands.