The clinicopathological and prognostic significance of autonomic nerves in salivary duct carcinoma

Manami Kajiwara¹, Hideaki Takahashi², Masato Nakaguro³, Daisuke Kawakita⁴, Hideaki Hirai¹, Yoshitaka Utsumi¹, Makoto Urano⁵, Yukiko Sato⁶, Kiyoaki Tsukahara⁷, Satoshi Kano⁸, Kenji Okami⁹, Hiroyuki Ozawa¹⁰, Keisuke Yamazaki¹¹, Takuro Okada¹², Akira Shimizu⁷, Kenji Hanyu⁷, Akihiro Sakai⁹, Mayu Yamauchi⁹, Mariko Sekimizu¹⁰, Toyoyuki Hanazawa¹³, Yuki Saito¹⁴, Yushi Ueki¹⁵, Yoshitaka Honma¹⁶, Tomoyuki Arai¹³, Sho Iwaki⁴, Koji Yamamura¹⁴, Yorihisa Imanishi¹⁰, Yuichiro Sato¹¹, Yuichiro Tada¹⁷, Toshitaka Nagao¹⁸; Multi-institutional Joint SDC Study Group in Japan

Affiliations

¹ Department of Anatomic Pathology, Tokyo Medical University, Shinjuku-Ku, Tokyo, Japan.
² Department of Otorhinolaryngology, Head and Neck Surgery, School of Medicine, Yokohama City University, Yokohama, Japan.
³ Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya, Japan.
⁴ Department of Otorhinolaryngology, Head and Neck Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
⁵ Department of Diagnostic Pathology, School of Medicine, Bantane Hospital, Fujita Health University, Nakagawa-Ku, Nagoya, Japan.
⁶ Division of Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-Ku, Tokyo, Japan.
⁷ Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University, Shinjuku-Ku, Tokyo, Japan.
⁸ Department of Otolaryngology - Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
⁹ Department of Otolaryngology, Head and Neck Surgery, School of Medicine, Tokai University, Isehara, Japan.
¹⁰ Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine, Shinjuku-Ku, Tokyo, Japan.
¹¹ Department of Head and Neck Surgery, Niigata Cancer Center Hospital, Niigata, Japan.
¹² Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University Hachioji Medical Center, Hachioji, Japan.
¹³ Department of Otorhinolaryngology/Head & Neck Surgery, Chiba University Graduate School of Medicine, Chuo-Ku, Chiba, Japan.
¹⁴ Department of Otolaryngology - Head and Neck Surgery, Faculty of Medicine, The University of Tokyo, Bunkyo-Ku, Tokyo, Japan.
¹⁵ Department of Otolaryngology Head and Neck Surgery, Niigata University Graduate School of Medical and Dental Sciences, Chuo-Ku, Niigata, Japan.
¹⁶ Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Chuo-Ku, Tokyo, Japan.
¹⁷ Department of Head and Neck Oncology and Surgery, International University of Health and Welfare, Mita Hospital, Minato-Ku, Tokyo, Japan.
¹⁸ Department of Anatomic Pathology, Tokyo Medical University, Shinjuku-Ku, Tokyo, Japan. nagao-t@tokyo-med.ac.jp.

PMID: 39042207
DOI: 10.1007/s00428-024-03873-x

The clinicopathological and prognostic significance of autonomic nerves in salivary duct carcinoma

Manami Kajiwara et al. Virchows Arch. 2024 Sep.

. 2024 Sep;485(3):439-452.

doi: 10.1007/s00428-024-03873-x. Epub 2024 Jul 23.

Authors

Affiliations

¹ Department of Anatomic Pathology, Tokyo Medical University, Shinjuku-Ku, Tokyo, Japan.
² Department of Otorhinolaryngology, Head and Neck Surgery, School of Medicine, Yokohama City University, Yokohama, Japan.
³ Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya, Japan.
⁴ Department of Otorhinolaryngology, Head and Neck Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
⁵ Department of Diagnostic Pathology, School of Medicine, Bantane Hospital, Fujita Health University, Nakagawa-Ku, Nagoya, Japan.
⁶ Division of Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-Ku, Tokyo, Japan.
⁷ Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University, Shinjuku-Ku, Tokyo, Japan.
⁸ Department of Otolaryngology - Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
⁹ Department of Otolaryngology, Head and Neck Surgery, School of Medicine, Tokai University, Isehara, Japan.
¹⁰ Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine, Shinjuku-Ku, Tokyo, Japan.
¹¹ Department of Head and Neck Surgery, Niigata Cancer Center Hospital, Niigata, Japan.
¹² Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University Hachioji Medical Center, Hachioji, Japan.
¹³ Department of Otorhinolaryngology/Head & Neck Surgery, Chiba University Graduate School of Medicine, Chuo-Ku, Chiba, Japan.
¹⁴ Department of Otolaryngology - Head and Neck Surgery, Faculty of Medicine, The University of Tokyo, Bunkyo-Ku, Tokyo, Japan.
¹⁵ Department of Otolaryngology Head and Neck Surgery, Niigata University Graduate School of Medical and Dental Sciences, Chuo-Ku, Niigata, Japan.
¹⁶ Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Chuo-Ku, Tokyo, Japan.
¹⁷ Department of Head and Neck Oncology and Surgery, International University of Health and Welfare, Mita Hospital, Minato-Ku, Tokyo, Japan.
¹⁸ Department of Anatomic Pathology, Tokyo Medical University, Shinjuku-Ku, Tokyo, Japan. nagao-t@tokyo-med.ac.jp.

PMID: 39042207
DOI: 10.1007/s00428-024-03873-x

Abstract

Many researchers have focused on the role of the autonomic nervous system in the tumor microenvironment. Autonomic nerves include the sympathetic and parasympathetic nerves, which are known to induce cancer growth and metastasis. However, in salivary duct carcinoma (SDC), a rare and highly malignant tumor, the issue should be investigated from both biological and therapeutic perspectives. We explored the clinicopathological and prognostic implications of the autonomic nerves in 129 SDCs. Immunohistochemistry was performed to determine the nature of each nerve using antibodies against S100, tyrosine hydroxylase (TH) as a sympathetic marker, and vesicular acetylcholine transporter (VAChT) as a parasympathetic marker. The area of each marker-positive nerve was digitized and evaluated quantitatively. Double immunofluorescence for TH and VAChT was performed in selected cases. The expression of the secreted neurotrophins was also examined. S100-positive nerves were present in the cancer tissue in 94 of 129 cases (72.9%). Among them, TH-positive sympathetic nerves and/or VAChT-positive parasympathetic nerves were identified in 92 cases (97.9%), and 59 cases (62.8%) had TH/VAChT-co-expressing nerves. Double immunofluorescence revealed a mosaic pattern of sympathetic and parasympathetic fibers in co-expressing nerve bundles. The presence of autonomic nerves, regardless of their area, was significantly associated with aggressive histological features, advanced T/N classification, and a poor prognosis, with shorter disease-free and overall survival. There was an association between some tumor immune microenvironment-related markers and the autonomic nerve status, but not the latter and the secreted neurotrophin expression. This study suggests that autonomic nerves might play a role in the progression of SDC.

Keywords: Autonomic nerve; Cancer neuroscience; Parasympathetic nerve; Salivary duct carcinoma; Sympathetic nerve; Tumor microenvironment.

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References

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The clinicopathological and prognostic significance of autonomic nerves in salivary duct carcinoma

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The clinicopathological and prognostic significance of autonomic nerves in salivary duct carcinoma

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