Subsets of salivary duct carcinoma defined by morphologic evidence of pleomorphic adenoma, PLAG1 or HMGA2 rearrangements, and common genetic alterations. Issue 20 (5th July 2016)

• Record Type: Journal Article
• Authors: Chiosea, Simion I.; Thompson, Lester D. R.; Weinreb, Ilan; Bauman, Julie E.; Mahaffey, Alyssa M.; Miller, Caitlyn; Ferris, Robert L.; Gooding, William E.
• Is Part Of: Cancer. Volume 122:Issue 20(2016)
• Page Start: 3136
• Page End: 3144
• Publication Date: 2016-07-05
• Subjects: malignant transformation -- next‐generation sequencing -- pleomorphic adenoma -- salivary -- salivary duct carcinoma; Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.30179
• Languages: English
• ISSNs: 0008-543X

Abstract

Abstract : 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 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). 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 . © 2016 American Cancer Society . Abstract : On the basis of morphologic and molecular evidence ( PLAG1 and HMGA2 status) of pleomorphic adenoma, 4 subsets of salivary duct carcinoma are identified that have distinct distributions of potentially targetable genetic alterations. Next‐generation sequencing reveals that de novo salivary duct carcinomas are characterized by combined HRAS / PIK3CA mutations and an absence of ERBB2 copy number gain.