title: An analysis of PLAG1 and HMGA2 rearrangements in salivary duct carcinoma and examination of the role of precursor lesions.
abstract: OBJECTIVE
  Salivary duct carcinoma (SDC) often arises in pleomorphic adenoma (PA). Putative precursors, including low-grade cribriform cystadenocarcinoma (LGCCC) and ductal carcinoma in-situ (DCIS), are more controversial. Rearrangement of PLAG1 or HMGA2 is seen in 50-70% of PAs, but this has not been investigated in SDC. Using a large collection of SDCs from a single institution, we aimed to study these genes by fluorescence in-situ hybridization (FISH), and to correlate the presence of precursor lesions/intraductal proliferations with gene alterations.
  
  
  RESULTS
  Forty-four SDCs were stained for smooth muscle actin, CK14, and p63, and examined with PLAG1 and HMGA2 FISH. Eight cases were SDC ex-PA; ten had a hyalinized nodule (HN), which is suspicious for PA; six arose in association with LGCCC; and twenty were 'de-novo' SDCs. Ten cases had PLAG1 rearrangement/amplification (22.7%) and eight had HMGA2 (18.2%) rearrangement/amplification. The positive cases were four SDC ex-PAs, eight SDCs with an HN, and five 'de-novo' SDCs. Twenty-three SDC ex-PAs were present in total (52.3%). All six SDC ex-LGCCCs were FISH-negative. Myoepithelial staining surrounded all LGCCCs, and demonstrated DCIS in 17 cases. Eleven DCIS lesions were in SDC ex-PAs or FISH-positive 'de-novo' SDCs. These cases represent 'cancerization' of ducts. Only six FISH-negative 'de-novo' SDCs showed DCIS.
  
  
  CONCLUSIONS
  A large proportion of SDCs arise in PAs (with or without residual evidence of a PA). A small proportion of SDCs arise in LGCCCs. Cases showing DCIS often represent cancerization.
authors.affiliation: Department of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Armita
authors.initials: A
authors.lastname: Bahrami
authors.forename: Bayardo
authors.initials: B
authors.lastname: Perez-Ordonez
authors.forename: James D
authors.initials: JD
authors.lastname: Dalton
authors.forename: Ilan
authors.initials: I
authors.lastname: Weinreb
mesh_terms: D000199:Actins / Q000378:metabolism; D008949:Adenoma, Pleomorphic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002278:Carcinoma in Situ / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D044584:Carcinoma, Ductal / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003536:Cystadenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D015321:Gene Rearrangement; D025743:HMGA2 Protein / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053547:Keratin-14 / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D018987:Salivary Ducts; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; C081876:CKAP4 protein, human; D004268:DNA-Binding Proteins; D025743:HMGA2 Protein; D053547:Keratin-14; D008565:Membrane Proteins; C104382:PLAG1 protein, human
keywords: HMGA2; PLAG1; ductal carcinoma in situ; low-grade cribriform cystadenocarcinoma; pleomorphic adenoma; precursor; salivary duct carcinoma