The high expression of FOXA1 is correlated with a favourable prognosis in salivary duct carcinomas: a study of 142 cases

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

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Aims: Salivary duct carcinoma (SDC) is an uncommon, aggressive tumour that, histologically, resembles high-grade mammary ductal carcinoma, and is characterised by the expression of androgen receptor (AR). The androgen signalling pathway, a potential therapeutic target, can be regulated by FOXA1. This study aimed to evaluate the clinicopathological implications of FOXA1 in SDC. Methods and results: We examined the relationship between the immunoexpression of FOXA1 and FOXA1 mutations and clinicopathological factors, including the biomarker status and clinical outcome, in 142 SDCs. FOXA1 was expressed in 128 SDCs (90.1%); the immunoexpression was heterogeneous. SDCs with a higher FOXA1 labelling index (LI) (≥20%) more frequently showed less advanced tumors on T classification (P = 0.002). FOXA1 LI was correlated positively with the AR expression value (r = 0.430, P < 0.001). PI3K and p-mTOR positivity, and intact-PTEN, were associated with a higher FOXA1 LI. Twenty-two of 121 SDCs (18.2%) harboured FOXA1 gene mutations at the flanking regions in and around the forkhead DNA binding domain; however, the given gene mutation and the expression of FOXA1 were not significantly correlated. A multivariate analysis revealed that SDCs with a higher FOXA1 LI were associated with longer overall survival and progression-free survival (P = 0.029 and 0.016, respectively). Conclusions: In SDC, FOXA1, which may biologically interact with the AR and PI3K signalling pathways, is a putative biomarker that may be associated with a favourable prognosis. Further studies are needed to apply the findings to the development of targeted personalised therapy for patients with SDC.

Original languageEnglish
Pages (from-to)943-952
Number of pages10
JournalHistopathology
Volume73
Issue number6
DOIs
Publication statusPublished - 12-2018

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Histology

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    Urano, M., Hirai, H., Tada, Y., Kawakita, D., Shimura, T., Tsukahara, K., Kano, S., Ozawa, H., Okami, K., Sato, Y., Fushimi, C., Shimizu, A., Takase, S., Okada, T., Sato, H., Imanishi, Y., Otsuka, K., Watanabe, Y., Sakai, A., ... Nagao, T. (2018). The high expression of FOXA1 is correlated with a favourable prognosis in salivary duct carcinomas: a study of 142 cases. Histopathology, 73(6), 943-952. https://doi.org/10.1111/his.13706