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Research Papers:

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 Ebisumoto, Takafumi Togashi, Yushi Ueki, Hisayuki Ota, Toyoyuki Hanazawa, Hideaki Chazono, Robert Yoshiyuki Osamura and Toshitaka Nagao _

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Oncotarget. 2017; 8:59023-59035. https://doi.org/10.18632/oncotarget.19812

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Abstract

Soichiro Takase1,2,*, Satoshi Kano3,*, Yuichiro Tada4,*, Daisuke Kawakita5, Tomotaka Shimura2,6, Hideaki Hirai2, Kiyoaki Tsukahara1, Akira Shimizu1, Yorihisa Imanishi7, Hiroyuki Ozawa7, Kenji Okami8, Yuichiro Sato9, Yukiko Sato10, Chihiro Fushimi4, Takuro Okada1, Hiroki Sato1, Kuninori Otsuka7, Yoshihiro Watanabe7, Akihiro Sakai8, Koji Ebisumoto8, Takafumi Togashi9, Yushi Ueki9, Hisayuki Ota9, Toyoyuki Hanazawa11, Hideaki Chazono11, Robert Yoshiyuki Osamura12 and Toshitaka Nagao2

1Department of Otolaryngology Head and Neck Surgery, Tokyo Medical University, Tokyo, Japan

2Department of Anatomic Pathology, Tokyo Medical University, Tokyo, Japan

3Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan

4Department of Head and Neck Oncology and Surgery, International University of Health and Welfare Mita Hospital, Tokyo, Japan

5Department of Otolaryngology Head and Neck Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

6Department of Otorhinolaryngology, Showa University School of Medicine, Tokyo, Japan

7Department of Otorhinolaryngology-Head and Neck Surgery, Keio University School of Medicine, Tokyo, Japan

8Department of Otolaryngology Head and Neck Surgery, Tokai University School of Medicine, Isehara, Japan

9Department of Head and Neck Surgery, Niigata Cancer Center Hospital, Niigata, Japan

10Department of Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan

11Department of Otolaryngology, Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan

12Diagnostic Pathology Center, International University of Health and Welfare Mita Hospital, Tokyo, Japan

*These authors contributed equally to this work

Correspondence to:

Toshitaka Nagao, email: nagao-t@tokyo-med.ac.jp

Keywords: salivary duct carcinoma, androgen receptor, p53, CK5/6, HER2

Received: June 22, 2017     Accepted: July 26, 2017     Published: August 02, 2017

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.


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