Abstract 653: A comparative analysis of pathological features and molecular genetics between salivary duct carcinoma and adenocarcinoma, not otherwise specified

Abstract

Abstract Salivary duct carcinoma (SDC), an aggressive subtype of malignant salivary gland tumors with distinct histopathological features, is often characterized by over-expression of androgen receptor (AR) and HER2. Adenocarcinoma, not otherwise specified (ANOS), is another subtype with ductal differentiation without diagnostic histopathological features. The aim of this study was to compare the pathological features and genetic alterations (GAs) between SDC and ANOS. We reviewed the 128 pathologically confirmed major salivary gland carcinoma cases and found 15 SDC and 20 ANOS cases, and each of 15 specimens were available for this comparative analysis. The clinicopathological characteristics of the 30 cases were retrospectively reviewed. Immunohisitochemical (IHC) analysis including AR, GCDFP-15, HER2, etc. was performed. Next generation sequencing (NGS) was performed, using multiplex PCR for enrichment of cancer related gene loci covering hotspots of 50 cancer genes. There were 22 men and 8 women with a median age of 64 years (range, 18-87). The main results summarized in the table below. On IHC analysis, SDC and AR positive (+ve) ANOS showed distinct over-expression of GCDFP-15 and HER2. HER2 amplification (FISH) was detected only in SDC and AR +ve ANOS. The most frequent GAs was observed in TP53, followed by genes involved in PI3K-AKT-mTOR pathway and ERBB2. These frequencies were similar between SDC and AR +ve ANOS. In survival analysis among 25 advanced cases with definitive surgery, AR +ve ANOS appeared to have poorer prognosis than AR -ve ANOS. Univariate analysis revealed that HER2-positivity (IHC 3+, FISH positive, or both) tended to have a poorer prognosis (hazard ratio 3.2, 95% confidence interval, 1.0-10.6). In conclusion, we found similarity in clinicopathological features and GAs between SDC and AR +ve ANOS. Screening AR and HER2 for ANOS is critical due to the therapeutic and prognostic considerations, as is SDC. Immunohisitochemical patterns, genomic alterations, and clinical outcomesSDCAR +ve ANOSAR -ve ANOSIHC (N=30)Estrogen receptor (%)2/15 (13)1/9 (11)0/6 (0)Progesterone receptor (%)3/15 (20)3/9 (33)0/6 (0)Androgen receptor (%)15/15 (100)9/9 (100)0/6 (0)Prolactin (%)0/15 (0)0/9 (0)0/6 (0)GCDFP-15 (%)14/15 (93)8/9 (88)0/6 (0)PSA (%)4/15 (27)0/9 (0)0/6 (0)HER2 ≥ 2+ (%)8/15 (53)8/9 (88)0/6 (0)EGFR ≥ 2+ (%)9/15 (60)9/9 (100)5/6 (83)Ki-67 > 30% (%)7/8 (87)3/6 (50)2/5 (40)FISH (N=26)HER2 (%)5/14 (36)4/7 (57)0/5 (0)NGS (N=29)TP53 (%)3/15 (20)2/8 (25)2/6 (33)PI3K-AKT-mTOR pathway (%)3/15 (20)2/8 (25)0/3 (0)ERBB2 (%)2/15 (14)2/8 (25)0/6 (0)Survival analysis (N=25)5-year overall survival61% (N=14)29% (N=8)75% (N=3)5-year recurrence-free survival64% (N=14)14% (N=8)50% (N=3) Citation Format: Yoshinori Imamura, Naomi Kiyota, Ken-ichi Nibu, Chihoko Ikeda, Tomoo Itoh, Ryohei Sasaki, Kazuko Sakai, Kazuto Nishio, Masanori Toyoda, Hironobu Minami, Naoki Otsuki. A comparative analysis of pathological features and molecular genetics between salivary duct carcinoma and adenocarcinoma, not otherwise specified [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 653.