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PIK3CA Mutations and PTEN Loss in Salivary Duct Carcinomas

Griffith, Christopher C. MD, PhD; Seethala, Raja R. MD; Luvison, Alyssa BS; Miller, Megan BS; Chiosea, Simion I. MD

American Journal of Surgical Pathology:
doi: 10.1097/PAS.0b013e3182880d5a
Original Articles
Abstract

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.

Author Information

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: chioseasi@upmc.edu).

© 2013 by Lippincott Williams & Wilkins.