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 Ebisumoto & 8 others Takafumi Togashi, Yushi Ueki, Hisayuki Ota, Yukiko Sato, Natsuki Saigusa, Masato Nakaguro, Toyoyuki Hanazawa, Toshitaka Nagao

Research output: Contribution to journalArticle

1 Citation (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 - 2018 Dec 1

Fingerprint

Salivary Ducts
Androgen Receptors
Carcinoma
Phosphatidylinositol 3-Kinases
Mutation
Biomarkers
Carcinoma, Ductal, Breast
Androgens
Disease-Free Survival
Neoplasms
Multivariate Analysis
Gene Expression
Survival
DNA
Therapeutics
Genes

Keywords

  • androgen receptor
  • FOXA1
  • PI3K signalling pathway
  • salivary duct carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

Cite this

Urano, M., Hirai, H., Tada, Y., Kawakita, D., Shimura, T., Tsukahara, K., ... 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

The high expression of FOXA1 is correlated with a favourable prognosis in salivary duct carcinomas : a study of 142 cases. / Urano, Makoto; Hirai, Hideaki; Tada, Yuichiro; Kawakita, Daisuke; Shimura, Tomotaka; Tsukahara, Kiyoaki; Kano, Satoshi; Ozawa, Hiroyuki; Okami, Kenji; Sato, Yuichiro; Fushimi, Chihiro; Shimizu, Akira; Takase, Soichiro; Okada, Takuro; Sato, Hiroki; Imanishi, Yorihisa; Otsuka, Kuninori; Watanabe, Yoshihiro; Sakai, Akihiro; Ebisumoto, Koji; Togashi, Takafumi; Ueki, Yushi; Ota, Hisayuki; Sato, Yukiko; Saigusa, Natsuki; Nakaguro, Masato; Hanazawa, Toyoyuki; Nagao, Toshitaka.

In: Histopathology, Vol. 73, No. 6, 01.12.2018, p. 943-952.

Research output: Contribution to journalArticle

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, Ebisumoto, K, Togashi, T, Ueki, Y, Ota, H, Sato, Y, Saigusa, N, Nakaguro, M, Hanazawa, T & Nagao, T 2018, 'The high expression of FOXA1 is correlated with a favourable prognosis in salivary duct carcinomas: a study of 142 cases', Histopathology, vol. 73, no. 6, pp. 943-952. https://doi.org/10.1111/his.13706
Urano, Makoto ; Hirai, Hideaki ; Tada, Yuichiro ; Kawakita, Daisuke ; Shimura, Tomotaka ; Tsukahara, Kiyoaki ; Kano, Satoshi ; Ozawa, Hiroyuki ; Okami, Kenji ; Sato, Yuichiro ; Fushimi, Chihiro ; Shimizu, Akira ; Takase, Soichiro ; Okada, Takuro ; Sato, Hiroki ; Imanishi, Yorihisa ; Otsuka, Kuninori ; Watanabe, Yoshihiro ; Sakai, Akihiro ; Ebisumoto, Koji ; Togashi, Takafumi ; Ueki, Yushi ; Ota, Hisayuki ; Sato, Yukiko ; Saigusa, Natsuki ; Nakaguro, Masato ; Hanazawa, Toyoyuki ; Nagao, Toshitaka. / The high expression of FOXA1 is correlated with a favourable prognosis in salivary duct carcinomas : a study of 142 cases. In: Histopathology. 2018 ; Vol. 73, No. 6. pp. 943-952.
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T1 - The high expression of FOXA1 is correlated with a favourable prognosis in salivary duct carcinomas

T2 - a study of 142 cases

AU - Urano, Makoto

AU - Hirai, Hideaki

AU - Tada, Yuichiro

AU - Kawakita, Daisuke

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 - 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 - Sato, Yukiko

AU - Saigusa, Natsuki

AU - Nakaguro, Masato

AU - Hanazawa, Toyoyuki

AU - Nagao, Toshitaka

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

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