Biomarker immunoprofile in salivary duct carcinomas: Clinicopathological and prognostic implications with evaluation of the revised classification

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

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Salivary duct carcinoma (SDC) is an uncommon, aggressive malignant neoplasm histologically resembling high-grade mammary ductal carcinoma. SDC can arise de novo or ex pleomorphic adenoma. To clarify the correlation of biomarker immunoprofile with clinicopathological findings and clinical outcome of SDC, we conducted immunohistochemistry for EGFR, HER2, HER3, AR, CK5/6, p53, and Ki-67, along with HER2 fluorescence in situ hybridization in 151 SDCs. SDCs ex pleomorphic adenoma more commonly overexpressed EGFR, HER2, HER3, and Ki-67 than de novo SDCs (P = 0.015, < 0.001, 0.045, and 0.02, respectively). In multivariate analysis, AR- and CK5/6+ were associated with shorter progression-free survival (P = 0.027 and 0.004, respectively). Moreover, patients with p53-extreme negative/positive demonstrated poorer overall survival (P = 0.007). On assessing the revised classification by the combination of biomarker expression, the percentages of each subtype were as follows: 'apocrine A' (AR+/HER2-/Ki-67-low) (24%), 'apocrine B' (AR+/HER2-/Ki-67-high) (18%), 'apocrine HER2' (AR+/HER2+) (35%), 'HER2-enriched' (AR-/HER2+) (12%), and 'double negative' (AR-/HER2-) (11%). 'Double negative' was further subclassified into 'basal-like' (EGFR and/or CK5/6+) (7%) and 'unclassified' (3%). Consequently, patients with 'apocrine A' showed a better progression-free survival than those with any other subtypes. Our revised immunoprofiling classification was valuable for predicting the survival and might be useful in personalized therapy for patients with SDC.

Original languageEnglish
Pages (from-to)59023-59035
Number of pages13
JournalOncotarget
Volume8
Issue number35
DOIs
Publication statusPublished - 2017

Keywords

  • Androgen receptor
  • CK5/6
  • HER2
  • P53
  • Salivary duct carcinoma

ASJC Scopus subject areas

  • Oncology

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    Takase, S., Kano, S., Tada, Y., Kawakita, D., Shimura, T., Hirai, H., Tsukahara, K., Shimizu, A., Imanishi, Y., Ozawa, H., Okami, K., Sato, Y., Sato, Y., Fushimi, C., Okada, T., Sato, H., Otsuka, K., Watanabe, Y., Sakai, A., ... Nagao, T. (2017). Biomarker immunoprofile in salivary duct carcinomas: Clinicopathological and prognostic implications with evaluation of the revised classification. Oncotarget, 8(35), 59023-59035. https://doi.org/10.18632/oncotarget.19812