title: PLAG1 alteration in carcinoma ex pleomorphic adenoma: immunohistochemical and fluorescence in situ hybridization studies of 22 cases.
abstract: Carcinoma ex pleomorphic adenoma (CA-ex-PA) may arise with nearly any histologic subtype of carcinoma of the salivary gland. In the absence of recognizable residual pleomorphic adenoma (PA) or a prior history of PA, distinction of CA-ex-PA from morphologically similar de novo carcinomas may be difficult. Oncogenic rearrangement of PLAG1 (pleomorphic adenoma gene 1) has been established in PA; however, it has not yet been proven that PLAG1 alteration persists in carcinomas developed from preceding PA. We evaluated 22 histologically diverse CA-ex-PA by immunohistochemistry for PLAG1, and/or by FISH targeting PLAG1. Of these, 17 cases were immunoreactive (1+ to 3+) and 5 were immunonegative/rare positive for PLAG1. For comparison, 39 various salivary gland neoplasms were immunostained for PLAG1, of which all scored negative/rare positive. Twelve of 19 CA-ex-PA analyzed by PLAG1 FISH (63 %) were positive for gene rearrangement, 2 showed only a trisomy/polysomy profile, and 5 had a normal pattern. One FISH-positive tumor showed amplification of PLAG1. One of 3 cases analyzed for HMGA2 FISH was positive for gene rearrangement. In our series, the majority of CA-ex-PA harbored altered PLAG1 or HMGA2 genes detectable by FISH. While PLAG1 immunostain was specific for CA-ex-PA against other carcinomas, its application as a standalone discriminatory test was limited by variable expression. We conclude that most CA-ex-PA, regardless of morphologic subtype, carry altered PLAG1 or HMGA2 genes, and that FISH for PLAG1, along with immunohistochemistry for PLAG1, may help discriminate CA-ex-PA from its de novo carcinoma counterpart.
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. armita.bahrami@stjude.org
authors.forename: Armita
authors.initials: A
authors.lastname: Bahrami
authors.forename: James D
authors.initials: JD
authors.lastname: Dalton
authors.forename: Bangalore
authors.initials: B
authors.lastname: Shivakumar
authors.forename: Jeffrey F
authors.initials: JF
authors.lastname: Krane
mesh_terms: D008949:Adenoma, Pleomorphic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D025743:HMGA2 Protein / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; D025743:HMGA2 Protein; C104382:PLAG1 protein, human