The clinicopathological significance of the adipophilin and fatty acid synthase expression in salivary duct carcinoma

Hideaki Hirai, Yuichiro Tada, Masato Nakaguro, Daisuke Kawakita, Yukiko Sato, Tomotaka Shimura, Kiyoaki Tsukahara, Satoshi Kano, Hiroyuki Ozawa, Kenji Okami, Yuichiro Sato, Chihiro Fushimi, Akira Shimizu, Isaku Okamoto, Soichiro Takase, Takuro Okada, Hiroki Sato, Yorihisa Imanishi, Kuninori Otsuka, Yoshihiro WatanabeAkihiro Sakai, Koji Ebisumoto, Takafumi Togashi, Yushi Ueki, Hisayuki Ota, Natsuki Saigusa, Hideaki Takahashi, Mizuo Ando, Makoto Urano, Toyoyuki Hanazawa, Toshitaka Nagao

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalVirchows Archiv
DOIs
Publication statusAccepted/In press - 2020 Jan 1

Keywords

  • Adipophilin
  • Androgen receptor
  • Fatty acid synthase
  • Lipid metabolism
  • Prognosis
  • Salivary duct carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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    Hirai, H., Tada, Y., Nakaguro, M., Kawakita, D., Sato, Y., Shimura, T., Tsukahara, K., Kano, S., Ozawa, H., Okami, K., Sato, Y., Fushimi, C., Shimizu, A., Okamoto, I., Takase, S., Okada, T., Sato, H., Imanishi, Y., Otsuka, K., ... Nagao, T. (Accepted/In press). The clinicopathological significance of the adipophilin and fatty acid synthase expression in salivary duct carcinoma. Virchows Archiv. https://doi.org/10.1007/s00428-020-02777-w