Subsets of salivary duct carcinoma defined by morphologic evidence of pleomorphic adenoma, PLAG1 or HMGA2 rearrangements, and common genetic alterations.

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.

• Authors: Simion I Chiosea, Lester D R Thompson, Ilan Weinreb, Julie E Bauman, Alyssa M Mahaffey, Caitlyn Miller, Robert L Ferris, William E Gooding
• Journal: Cancer (Cancer) Vol. 122 Issue 20 Pg. 3136-3144 (Oct 15 2016) ISSN: 1097-0142 [Electronic] United States
• PMID: 27379604 (Publication Type: Journal Article)
• Copyright: © 2016 American Cancer Society.

Chemical References

• Biomarkers, Tumor
• DNA-Binding Proteins
• HMGA2 Protein
• PLAG1 protein, human

Topics

• Adenoma, Pleomorphic (diagnosis, genetics)
• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (genetics)
• Carcinoma, Ductal (classification, diagnosis, genetics)
• DNA-Binding Proteins (genetics)
• Diagnosis, Differential
• Female
• Follow-Up Studies
• Gene Rearrangement
• Genetic Variation (genetics)
• HMGA2 Protein (genetics)
• Humans
• Immunoenzyme Techniques
• In Situ Hybridization, Fluorescence
• Male
• Middle Aged
• Mutation
• Neoplasm Grading
• Neoplasm Staging
• Prognosis
• Salivary Gland Neoplasms (classification, diagnosis, genetics)
• Survival Rate