PMID- 27379604
OWN - NLM
STAT- MEDLINE
DCOM- 20170525
LR  - 20181113
IS  - 1097-0142 (Electronic)
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 122
IP  - 20
DP  - 2016 Oct 15
TI  - Subsets of salivary duct carcinoma defined by morphologic evidence of pleomorphic 
      adenoma, PLAG1 or HMGA2 rearrangements, and common genetic alterations.
PG  - 3136-3144
LID - 10.1002/cncr.30179 [doi]
AB  - BACKGROUND: The 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). 
      METHODS: SDCs (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. RESULTS: 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). 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 alpha (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). CONCLUSIONS: The 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. (c) 2016 American Cancer Society.
CI  - (c) 2016 American Cancer Society.
FAU - Chiosea, Simion I
AU  - Chiosea SI
AD  - Depatment of Pathology, University of Pittsburgh Medical Center, Pittsburgh, 
      Pennsylvania. chioseasi@upmc.edu.
FAU - Thompson, Lester D R
AU  - Thompson LD
AUID- ORCID: 0000-0003-3714-1432
AD  - Department of Pathology, Southern California Permanente Medical Group, Woodland 
      Hills, California.
FAU - Weinreb, Ilan
AU  - Weinreb I
AD  - Department of Pathology, University Health Network, Toronto, Ontario, Canada.
FAU - Bauman, Julie E
AU  - Bauman JE
AD  - Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, 
      Pennsylvania.
FAU - Mahaffey, Alyssa M
AU  - Mahaffey AM
AD  - Depatment of Pathology, University of Pittsburgh Medical Center, Pittsburgh, 
      Pennsylvania.
FAU - Miller, Caitlyn
AU  - Miller C
AD  - Depatment of Pathology, University of Pittsburgh Medical Center, Pittsburgh, 
      Pennsylvania.
FAU - Ferris, Robert L
AU  - Ferris RL
AUID- ORCID: 0000-0001-6605-2071
AD  - Division of Head and Neck Surgery, Department of Otolaryngology, University of 
      Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
FAU - Gooding, William E
AU  - Gooding WE
AD  - Biostatistics Facility, University of Pittsburgh Cancer Institute, Pittsburgh, 
      Pennsylvania.
LA  - eng
GR  - P30 CA047904/CA/NCI NIH HHS/United States
GR  - P50 CA097190/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20160705
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HMGA2 Protein)
RN  - 0 (PLAG1 protein, human)
SB  - IM
MH  - Adenoma, Pleomorphic/*diagnosis/genetics
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/*genetics
MH  - Carcinoma, Ductal/classification/*diagnosis/genetics
MH  - DNA-Binding Proteins/*genetics
MH  - Diagnosis, Differential
MH  - Female
MH  - Follow-Up Studies
MH  - *Gene Rearrangement
MH  - Genetic Variation/*genetics
MH  - HMGA2 Protein/*genetics
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Neoplasm Grading
MH  - Neoplasm Staging
MH  - Prognosis
MH  - Salivary Gland Neoplasms/classification/*diagnosis/genetics
MH  - Survival Rate
PMC - PMC5048512
MID - NIHMS796836
OTO - NOTNLM
OT  - malignant transformation
OT  - next-generation sequencing
OT  - pleomorphic adenoma
OT  - salivary
OT  - salivary duct carcinoma
COIS- None
EDAT- 2016/07/06 06:00
MHDA- 2017/05/26 06:00
PMCR- 2017/10/15
CRDT- 2016/07/06 06:00
PHST- 2016/04/22 00:00 [received]
PHST- 2016/05/28 00:00 [revised]
PHST- 2016/06/01 00:00 [accepted]
PHST- 2016/07/06 06:00 [pubmed]
PHST- 2017/05/26 06:00 [medline]
PHST- 2016/07/06 06:00 [entrez]
PHST- 2017/10/15 00:00 [pmc-release]
AID - 10.1002/cncr.30179 [doi]
PST - ppublish
SO  - Cancer. 2016 Oct 15;122(20):3136-3144. doi: 10.1002/cncr.30179. Epub 2016 Jul 5.