title: Strong expression of polypeptide N-acetylgalactosaminyltransferase 3 independently predicts shortened disease-free survival in patients with early stage oral squamous cell carcinoma.
abstract: The polypeptide N-acetylgalactosaminyltransferase (GalNAc-Ts) family of enzymes regulates the critical initial steps of mucin-type O-glycosylation. Among GalNAc-Ts that may significantly influence cancer biology, thus affecting cell differentiation, adhesion, invasion, and/or metastasis, GalNAc-T3 exhibits a high expression in several human cancers, closely associated with tumor progression and a poor prognosis. However, the expression pattern of GalNAc-T3 in oral squamous cell carcinoma (OSCC) remains obscure. Since postoperative recurrence of even early stage OSCC (ESOSCC) occurs at an early phase, significantly affecting their clinical course and worse outcome, the identification of clinically significant accurate biomarkers is needed. Therefore, we investigated the correlation between the immunohistochemical GalNAc-T3 expression and various clinicopathological characteristics and recurrence using 110 paraffin-embedded tumor samples obtained from patients with surgically resected ESOSCC (T1-2N0). Recurrence was recognized in 37 of 110 (33.6 %) patients. The GalNAc-T3 expression was considered to be strongly positive when 20 % or more of the cancer cells showed positive cytoplasmic staining. Consequently, a strong expression of GalNAc-T3 was observed in 40 patients (36.4 %), showing a close relationship to poor differentiation, the presence of lymphatic and vascular invasion, and recurrence. Univariate and multivariate analyses further demonstrated that the patients with a strong GalNAc-T3+ status had markedly lower disease-free survival (DFS) rates, especially within the first 2 years postoperatively. Therefore, GalNAc-T3 might play a role in the pathogenesis of ESOSCC recurrence, and its immunohistochemical detection potentially predicts a shorter DFS and may be a useful parameter for providing clinical management against ESOSCC in the early postoperative phase.
authors: Department of Pathology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.|Department of Dentistry and Oral Surgery, University Hospital of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
authors: Yoshikazu
authors: Y
authors: Harada
authors: Department of Occupational Pneumology, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
authors: Hiroto
authors: H
authors: Izumi
authors: Department of Pathology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
authors: Hirotsugu
authors: H
authors: Noguchi
authors: Department of Second Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
authors: Akihiro
authors: A
authors: Kuma
authors: Department of Health Policy and Management, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
authors: Yuichiro
authors: Y
authors: Kawatsu
authors: Department of Health Policy and Management, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
authors: Tomoko
authors: T
authors: Kimura
authors: Department of Pathology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.|Department of Urology, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
authors: Shohei
authors: S
authors: Kitada
authors: Second Department of Surgery, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
authors: Hidetaka
authors: H
authors: Uramoto
authors: Department of Pathology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.|Shared-Use Research Center, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
authors: Ke-Yong
authors: KY
authors: Wang
authors: Department of Pathology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.|Laboratory of Pathology, Fukuoka Wajiro Hospital, Fukuoka, 811-0213, Japan.
authors: Yasuyuki
authors: Y
authors: Sasaguri
authors: Department of Oral and Maxillofacial Surgery, Field of Oral and Maxillofacial Rehabilitation, Advanced Therapeutics Course, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Kagoshima, 890-8520, Japan.
authors: Hiroshi
authors: H
authors: Hijioka
authors: Department of Dentistry and Oral Surgery, University Hospital of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
authors: Akihiko
authors: A
authors: Miyawaki
authors: Department of Dentistry and Oral Surgery, University Hospital of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
authors: Ryoichi
authors: R
authors: Oya
authors: Department of Pathology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
authors: Toshiyuki
authors: T
authors: Nakayama
authors: Asahi-Matsumoto Hospital, Kitakyushu, 800-0242, Japan.
authors: Kimitoshi
authors: K
authors: Kohno
authors: Department of Pathology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan. sousuke@med.uoeh-u.ac.jp.|Institute of Pathology, Medical University of Graz, Graz, 8010, Austria. sousuke@med.uoeh-u.ac.jp.|Institute of Molecular Biosciences, University of Graz, Graz, 8010, Austria. sousuke@med.uoeh-u.ac.jp.
authors: Sohsuke
authors: http://orcid.org/0000-0003-2662-0024
authors: S
authors: Yamada
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality; D002448:Cell Adhesion; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000401:mortality; D017350:N-Acetylgalactosaminyltransferases / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D055815:Young Adult; D000097763:Polypeptide N-acetylgalactosaminyltransferase
chemical_list: D014408:Biomarkers, Tumor; D017350:N-Acetylgalactosaminyltransferases; D009363:Neoplasm Proteins; D000097763:Polypeptide N-acetylgalactosaminyltransferase
keywords: Disease-free survival (DFS); Early stage OSCC (ESOSCC); Oral squamous cell carcinoma (OSCC); Polypeptide N-acetylgalactosaminyltransferase 3 (GalNAc-T3); Vessel invasion