Abstract 4662: Expression of PLAG1 in salivary duct carcinomas: its efficacy of the distinction of carcinoma ex pleomorphic adenoma type and de novo type
Authors: Suzuki Takayoshi , Kano Satoshi , Hatanaka Kanako , Hatanaka Yutaka , Sakashita Tomohiro , Mizumachi Takatsugu , Hatakeyama Hiromitsu , Homma Akihiro , Matsuno Yoshihiro , Fukuda Satoshi 
Published: July 2017

Abstract
Salivary gland duct carcinoma (SDC) is one of the high-grade salivary gland carcinoma, classified into two patterns; i) carcinoma ex pleomorphic adenoma (Ca-ex-PA) type, which is derived from benign pleomorphic adenoma (PA), ii) de novo type, which is generated from normal salivary gland tissue. According to current WHO classification, Ca-ex-PA is diagnosed when pathological examination proves as follows, a) the mixture of the component of cancer cells and that of pre-existing PA cells, b) the existence of malignant cells after the resection of PA.
However, current criteria cannot entirely be accurate from the viewpoint of disease onset. For example, i) if a benign component of PA is replaced completely by Ca-ex-PA, the Ca-ex-PA type can be misdiagnosed as de novo type because histopathological examination cannot clarify the existence of PA in its surgery specimen. Moreover, ii) if a de novo type SDC, arising from normal salivary tissue, is growing and infiltrate to the preexisting PA, the de novo type can be misdiagnosed as Ca-ex-PA type.
Recently, Pleomorphic adenoma gene 1 (PLAG1) has been identified as the gene associated with tumorigenesis of PA. Subsequently, the overexpression of PLAG1 protein has been reported to be observed in both PAs and Ca-ex-PAs and useful for diagnosis of them.
Thus, we considered that PLAG1 immunohistochemistry can enable us to distinguish Ca-ex-PA type and de novo type in SDCs more definitively.
In this study, 23 SDC patients who underwent primary surgery for cancer at our institution were enrolled, including 14 Ca-ex-PA types and 9 de novo types. In each case, we had its formalin-fixed-paraffin-embedded tissue sample stained for PLAG1-antibodies (clone 3B7, Mouse mAb, 1:100, Abnova) and evaluated PLAG1 protein expression in the component of glandular-epithelial component and that of non-glandular-epithelial, respectively. PLAG1 immunostaining was scored as positive when the more than 10% nuclear staining of tumor cells are observed.
In all 23 SDCs, there was no PLAG1 protein overexpression in glandular-epithelial component, irrespective of benign or malignant. In all 14 Ca-ex-PA types, positive findings of PLAG1 overexpression were observed in non-glandular-epithelial component. In all 9 de novo types, no non-glandular-epithelial component showed any signs of PLAG1 protein overexpression. There was no discrepancy of conventional criteria and the status of PLAG1, which are the cases; i) Ca-ex-PA which is misdiagnosed as de novo type, ii) de novo type which is misdiagnosed as Ca-ex-PA type.
Conclusions : There is no difference between conventional criteria and PLAG1-based criteria in our cases. However, in the cases with obscure characteristics of PA morphologically, such as mucoid/myxoid or cartilaginous-like materials, findings of PLAG1-positive cells can help us to distinguish Ca-ex-PA type from de novo type more definitively.
Citation Format: Takayoshi Suzuki, Satoshi Kano, Kanako Hatanaka, Yutaka Hatanaka, Tomohiro Sakashita, Takatsugu Mizumachi, Hiromitsu Hatakeyama, Akihiro Homma, Yoshihiro Matsuno, Satoshi Fukuda. Expression of PLAG1 in salivary duct carcinomas: its efficacy of the distinction of carcinoma ex pleomorphic adenoma type and de novo type [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4662. doi:10.1158/1538-7445.AM2017-4662