TY - JOUR
T1 - The clinicopathological significance of the adipophilin and fatty acid synthase expression in salivary duct carcinoma
AU - Hirai, Hideaki
AU - Tada, Yuichiro
AU - Nakaguro, Masato
AU - Kawakita, Daisuke
AU - Sato, Yukiko
AU - Shimura, Tomotaka
AU - Tsukahara, Kiyoaki
AU - Kano, Satoshi
AU - Ozawa, Hiroyuki
AU - Okami, Kenji
AU - Sato, Yuichiro
AU - Fushimi, Chihiro
AU - Shimizu, Akira
AU - Okamoto, Isaku
AU - Takase, Soichiro
AU - Okada, Takuro
AU - Sato, Hiroki
AU - Imanishi, Yorihisa
AU - Otsuka, Kuninori
AU - Watanabe, Yoshihiro
AU - Sakai, Akihiro
AU - Ebisumoto, Koji
AU - Togashi, Takafumi
AU - Ueki, Yushi
AU - Ota, Hisayuki
AU - Saigusa, Natsuki
AU - Takahashi, Hideaki
AU - Ando, Mizuo
AU - Urano, Makoto
AU - Hanazawa, Toyoyuki
AU - Nagao, Toshitaka
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/8/1
Y1 - 2020/8/1
N2 - Salivary duct carcinoma (SDC) is an aggressive, uncommon tumor histologically comparable to high-grade mammary ductal carcinoma. SDCs are usually androgen receptor (AR)–positive and often HER2-positive. Recently, therapies targeting these molecules for SDC have attracted attention. Lipid metabolism changes have been described in association with biological behavior in various cancers, although no such relationship has yet been reported for SDC. We therefore analyzed the clinicopathological relevance of the immunohistochemical expression of adipophilin (ADP) and fatty acid synthase (FASN), representative lipid metabolism–related proteins, in 147 SDCs. ADP and FASN were variably immunoreactive in most SDCs (both 99.3%), and the ADP and FASN expression was negatively correlated (P = 0.014). ADP-positive (≥ 5%) SDCs more frequently exhibited a prominent nuclear pleomorphism and high-Ki-67 labeling index than those ADP-negative (P = 0.013 and 0.011, respectively). In contrast, a high FASN score, calculated by the staining proportion and intensity, (≥ 120) was correlated with the high expression of AR and FOXA1 (P < 0.001 and = 0.003, respectively). The ADP and FASN expression differed significantly among the subtypes based on biomarker immunoprofiling, as assessed by the AR, HER2, and Ki-67 status (P = 0.017 and 0.003, respectively). A multivariate analysis showed that ADP-positive expression was associated with a shorter overall and progression-free survival (P = 0.018 and 0.003, respectively). ADP was associated with an aggressive histopathology and unfavorable prognosis, and FASN may biologically interact with the AR signaling pathway in SDC. ADP may, therefore, be a new prognostic indicator and therapeutic target in SDC.
AB - Salivary duct carcinoma (SDC) is an aggressive, uncommon tumor histologically comparable to high-grade mammary ductal carcinoma. SDCs are usually androgen receptor (AR)–positive and often HER2-positive. Recently, therapies targeting these molecules for SDC have attracted attention. Lipid metabolism changes have been described in association with biological behavior in various cancers, although no such relationship has yet been reported for SDC. We therefore analyzed the clinicopathological relevance of the immunohistochemical expression of adipophilin (ADP) and fatty acid synthase (FASN), representative lipid metabolism–related proteins, in 147 SDCs. ADP and FASN were variably immunoreactive in most SDCs (both 99.3%), and the ADP and FASN expression was negatively correlated (P = 0.014). ADP-positive (≥ 5%) SDCs more frequently exhibited a prominent nuclear pleomorphism and high-Ki-67 labeling index than those ADP-negative (P = 0.013 and 0.011, respectively). In contrast, a high FASN score, calculated by the staining proportion and intensity, (≥ 120) was correlated with the high expression of AR and FOXA1 (P < 0.001 and = 0.003, respectively). The ADP and FASN expression differed significantly among the subtypes based on biomarker immunoprofiling, as assessed by the AR, HER2, and Ki-67 status (P = 0.017 and 0.003, respectively). A multivariate analysis showed that ADP-positive expression was associated with a shorter overall and progression-free survival (P = 0.018 and 0.003, respectively). ADP was associated with an aggressive histopathology and unfavorable prognosis, and FASN may biologically interact with the AR signaling pathway in SDC. ADP may, therefore, be a new prognostic indicator and therapeutic target in SDC.
KW - Adipophilin
KW - Androgen receptor
KW - Fatty acid synthase
KW - Lipid metabolism
KW - Prognosis
KW - Salivary duct carcinoma
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U2 - 10.1007/s00428-020-02777-w
DO - 10.1007/s00428-020-02777-w
M3 - Article
C2 - 32103349
AN - SCOPUS:85080033853
SN - 0945-6317
VL - 477
SP - 291
EP - 299
JO - Virchows Archiv
JF - Virchows Archiv
IS - 2
ER -