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

// Soichiro Takase 1, 2, * , Satoshi Kano 3, * , Yuichiro Tada 4, * , Daisuke Kawakita 5 , Tomotaka Shimura 2, 6 , Hideaki Hirai 2 , Kiyoaki Tsukahara 1 , Akira Shimizu 1 , Yorihisa Imanishi 7 , Hiroyuki Ozawa 7 , Kenji Okami 8 , Yuichiro Sato 9 , Yukiko Sato 10 , Chihiro Fushimi 4 , Takuro Okada 1 , Hiroki Sato 1 , Kuninori Otsuka 7 , Yoshihiro Watanabe 7 , Akihiro Sakai 8 , Koji Ebisumoto 8 , Takafumi Togashi 9 , Yushi Ueki 9 , Hisayuki Ota 9 , Toyoyuki Hanazawa 11 , Hideaki Chazono 11 , Robert Yoshiyuki Osamura 12 and Toshitaka Nagao 2 1 Department of Otolaryngology Head and Neck Surgery, Tokyo Medical University, Tokyo, Japan 2 Department of Anatomic Pathology, Tokyo Medical University, Tokyo, Japan 3 Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan 4 Department of Head and Neck Oncology and Surgery, International University of Health and Welfare Mita Hospital, Tokyo, Japan 5 Department of Otolaryngology Head and Neck Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan 6 Department of Otorhinolaryngology, Showa University School of Medicine, Tokyo, Japan 7 Department of Otorhinolaryngology-Head and Neck Surgery, Keio University School of Medicine, Tokyo, Japan 8 Department of Otolaryngology Head and Neck Surgery, Tokai University School of Medicine, Isehara, Japan 9 Department of Head and Neck Surgery, Niigata Cancer Center Hospital, Niigata, Japan 10 Department of Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan 11 Department of Otolaryngology, Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan 12 Diagnostic 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.