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.Electronic supplementary materialThe online version of this article (doi:10.1007/s13277-015-3928-7) contains supplementary material, which is available to authorized users.
Highlights
Oral cancer is the most common head and neck cancer, which is the sixth most common malignancy worldwide, including in Japan
We show for the first time that, in patients with postoperative early stage OSCC (ESOSCC), a cytoplasmic strong GalNAc-T3 expression is significantly correlated with a shortened disease-free survival (DFS) and that this molecule might be a promising biomarker for the clinical management of ESOSCC
The current study showed for the first time that an immunohistochemically cytoplasmic strong GalNAc-T3positive expression is a powerful and independent negative indicator of DFS and potential worse outcome in patients with postoperative ESOSCC, especially within the first 2 years after surgery
Summary
Oral cancer is the most common head and neck cancer, which is the sixth most common malignancy worldwide, including in Japan. Approximately 264,000 new cases are diagnosed each year, with oral squamous cell carcinoma (OSCC) comprising more than 90 % histological types of these cases. Of these cases, more than 128,000 patients die of the disease annually, and the mortality rate of OSCC is 3.7 per 100,000 in Japan alone [1,2,3]. Even early stage OSCC (ESOSCC) lesions treated with surgery alone, which more than 80 % can be cured by therapy, may exhibit postoperative relapse within the first 2 to 3 years [6,7,8]. It is critical to predict which ESOSCC patients (T1–2N0) are prone to recurrence/metastasis and mortality after surgery using practically accurate biomarkers. The clinical picture of OSCC is significantly determined by the complex interplay among additional cellular alterations, e.g., epigenetic modulation of the gene expression, at least in part [1, 4]
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