Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
Am J Surg Pathol. 2013 Aug;37(8):1201-7. doi: 10.1097/PAS.0b013e3182880d5a.
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.
涎腺癌（SDC）是一种侵袭性恶性肿瘤，常表现为晚期。已知编码磷酸肌醇 3-激酶（PI3K）p110α催化亚基的基因突变/扩增和/或磷酸酶和张力蛋白同源物（PTEN）的缺失可激活磷酸肌醇 3-激酶（PI3K）途径，可能代表一个治疗靶点。在 34 例 SDC 中的 7 例（20.5%）中，SNaPshot 聚合酶链反应检测到 PIK3CA 外显子 9[p.E545K（n=3）和 p.E542K（n=2）]或外显子 20[p.H1047R（n=2）]突变。PIK3CA p.E545K 突变在 3 例具有常规形态的 SDC 中被鉴定出来。唯一一例具有间变性转化的 SDC 显示出 PIK3CA p.H1047R 突变，而在 2 例 SDC 中 p.E542K 突变中仅鉴定出 1 例。在 16 例测试的 SDC 中，均未通过荧光原位杂交检测到 PIK3CA 扩增。荧光原位杂交鉴定出 16 例测试的 SDC 中有 8 例（50%）PTEN 缺失[纯合缺失（n=3）、10 号染色体单体缺失（n=3）、杂合缺失（n=2）]。有 2 例同时显示 PIK3CA 突变和 PTEN 缺失，表明这些事件并非相互排斥。这些发现为 SDC 患者 PI3K 途径的治疗靶向提供了分子依据。
