PIK3CA Mutations and PTEN Loss in Salivary Duct CarcinomasGriffith, Christopher C. MD, PhD; Seethala, Raja R. MD; Luvison, Alyssa BS; Miller, Megan BS; Chiosea, Simion I. MDThe American Journal of Surgical Pathology: August 2013 - Volume 37 - Issue 8 - p 1201–1207 doi: 10.1097/PAS.0b013e3182880d5a Original Articles Abstract Author Information Salivary duct carcinoma (SDC) is an aggressive malignancy that frequently presents at an advanced stage. Mutations/amplification of the gene encoding the p110α catalytic subunit of phosphoinositide 3-kinase (PIK3CA) and/or loss of the phosphatase and tensin homolog (PTEN) are known to activate the phosphoinositide 3-kinase (PI3K) pathway and may represent a therapeutic target. In 7 of 34 SDCs (20.5%) a SNaPshot polymerase chain reaction detected PIK3CA exon 9 [p.E545K (n=3) and p.E542K (n=2)] or exon 20 [p.H1047R (n=2)] mutations. PIK3CA p.E545K mutation was identified in 3 de novo SDCs with conventional morphology. The only case of SDC with anaplastic transformation showed PIK3CA p.H1047R mutation, whereas 1 of 2 PIK3CA p.E542K mutations was identified in SDC arising in a pleomorphic adenoma. None of the 16 tested SDCs showed PIK3CA amplification by fluorescence in situ hybridization. Fluorescence in situ hybridization identified PTEN loss in 8 of 16 tested SDCs (50%) [homozygous deletion (n=3), chromosome 10 monosomy (n=3), hemizygous deletion (n=2)]. Two cases showed both PIK3CA mutation and PTEN loss, suggesting that these events are not mutually exclusive. These findings offer a molecular rationale for therapeutic targeting of the PI3K pathway in patients with SDC. Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Simion I. Chiosea, MD, Department of Pathology, University of Pittsburgh Medical Center, 200 Lothrop St, Pittsburgh, PA 15213 (e-mail: firstname.lastname@example.org). © 2013 by Lippincott Williams & Wilkins.