HMGA2 Immunoexpression is frequent in salivary gland pleomorphic adenoma: immunohistochemical and molecular analyses of PLAG1 and HMGA2 in 25 cases.

The main oncologic events in pleomorphic adenoma (PA) are the translocations of Pleomorphic adenoma gene 1 (PLAG1) on chromosome 8q12 and High-mobility group AT-hook 2 (HMGA2) on chromosome 12q14.3 with various fusion partners. These translocations result in the transcriptional up-regulation of PLAG1 and HMGA2 proteins. We carried out a preliminary evaluation of PLAG1 translocation by fluorescence in-situ hybridization (FISH), immunohistochemistry (IHC) and HMGA2 IHC on twenty-five archived formalin-fixed paraffin-embedded tissues of PAs and its clinicopathologic features. Only eight cases were successfully hybridized and 50% of the interpretable cases were considered positive for PLAG1 translocation. PLAG1 IHC was only positive in 2 (8%) of the 25 cases stained, including one of the positive PLAG1 translocation cases. HMGA2 IHC was positive in 12 (48%) of the 25 cases stained including 2 (50%) of the 4 cases identified with PLAG1 translocation by FISH, 3 (75%) of the 4 cases negative for PLAG1 translocation by FISH and 7 (41%) of the 17 cases with failed hybridization. Overall, 15 (60%) of the 25 PA cases demonstrated PLAG1 and/or HMGA2 alterations confirmed either by FISH or IHC. In conclusion, PLAG1 and HMGA2 alterations were confirmed either by FISH or IHC in this cohort and HMGA2 alteration is a common event in PAs of salivary gland. IJCEP