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Consistent PLAG1 and HMGA2 abnormalities distinguish carcinoma ex-pleomorphic adenoma from its de novo counterparts.

ABSTRACT: Carcinoma ex-pleomorphic adenoma (CA ex-PA) is a malignant salivary gland tumor that arises in association with pleomorphic adenoma (PA). Both PA and CA ex-PA have a broad spectrum of histology, and distinction from their histologic mimics may be difficult based on morphology alone. PLAG1 and HMGA2 abnormalities are the most common genetic events in both PA and CA ex-PA; however, the use of PLAG1 and HMGA2 as adjunct molecular tests has not been well established. Fluorescence in situ hybridization for PLAG1 and HMGA2 was performed on 22 CA ex-PA (10 myoepithelial carcinomas [MECAs], 10 salivary duct carcinomas [SDCs], 1 carcinoma with squamoglandular features, and 1 mixed MECA-adenocarcinoma not otherwise specified), 20 de novo carcinomas (11 MECAs and 9 SDCs), 16 PAs, and 11 PA-histologic mimics. All except 3 CAs ex-PA (86%) were positive for PLAG1 or HMGA2 rearrangements/amplifications. In contrast, 18 (90%) of 20 de novo carcinomas lacked abnormalities in PLAG1 or HMGA2 (P < .01). PLAG1 or HMGA2 rearrangements were identified in 6 (67%) of 9 hypocellular myxoid PAs and in 2 (29%) of 7 cellular PAs. Furthermore, all morphologic mimics of PA were negative for PLAG1 or HMGA2. PLAG1 and HMGA2 rearrangements are the most common genetic events in CA ex-PA regardless of the histologic subtype. Unlike CA ex-PA, de novo carcinomas were negative for PLAG1 and HMGA2. Interestingly, rearrangements of PLAG1/HMGA2 were identified in most hypocellular PAs but only in a small subset of cellular PAs. Fluorescence in situ hybridization for PLAG1 or HMGA2 can be used to distinguish between PA and CA ex-PA and their morphologic mimics.

SUBMITTER: Katabi N

PROVIDER: S-EPMC4768723 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Consistent PLAG1 and HMGA2 abnormalities distinguish carcinoma ex-pleomorphic adenoma from its de novo counterparts.

Katabi Nora N Ghossein Ronald R Ho Alan A Dogan Snjezana S Zhang Lei L Sung Yun-Shao YS Antonescu Cristina R CR

Human pathology 20140907 1

Carcinoma ex-pleomorphic adenoma (CA ex-PA) is a malignant salivary gland tumor that arises in association with pleomorphic adenoma (PA). Both PA and CA ex-PA have a broad spectrum of histology, and distinction from their histologic mimics may be difficult based on morphology alone. PLAG1 and HMGA2 abnormalities are the most common genetic events in both PA and CA ex-PA; however, the use of PLAG1 and HMGA2 as adjunct molecular tests has not been well established. Fluorescence in situ hybridizati ...[more]

PMID: 25439740

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Project description:BackgroundThe authors hypothesized that histogenetic classification of salivary duct carcinoma (SDC) could account for de novo tumors and those with morphologic or molecular evidence (pleomorphic adenoma gene 1 [PLAG1], high-mobility group AT hook 2 [HMGA2] rearrangement, amplification) of pleomorphic adenoma (PA).MethodsSDCs (n = 66) were reviewed for morphologic evidence of PA. PLAG1 and HMGA2 alterations were detected by fluorescence in situ hybridization (FISH). PLAG1-positive tumors were tested by FISH for fibroblast growth factor receptor 1 (FGFR1) rearrangement. Thirty-nine tumors were analyzed using a commercial panel for mutations and copy number variations in 50 cancer-related genes.ResultsOn 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). The median disease-free survival was 37 months (95% confidence interval, 28.4-45.6 months). Disease-free survival and other clinicopathologic parameters did not differ for the subsets defined above. Combined Harvey rat sarcoma viral oncogene homolog/phosphatidylinositol-4,5-biphosphate 3-kinase, catalytic subunit α (HRAS/PIK3CA) mutations were observed predominantly in de novo carcinomas (5 of 8 vs 2 of 31 tumors; P = .035). Erb-B2 receptor tyrosine kinase 2 (ERBB2) copy number gain was not observed in de novo carcinomas (0 of 8 vs 12 of 31 tumors; P = .08). Tumor protein 53 (TP53) mutations were more common in SDC ex pleomorphic adenomas than in de novo carcinomas (17 of 31 vs 1 of 8 tumors; P = .033).ConclusionsThe genetic profile of SDC varies with the absence or presence of pre-existing PA and its cytogenetic signature. Most de novo SDCs harbor combined HRAS/PIK3CA mutations and no ERBB2 amplification. Cancer 2016;122:3136-44. © 2016 American Cancer Society.

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Consistent PLAG1 and HMGA2 abnormalities distinguish carcinoma ex-pleomorphic adenoma from its de novo counterparts.

Publications

Consistent PLAG1 and HMGA2 abnormalities distinguish carcinoma ex-pleomorphic adenoma from its de novo counterparts.

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