Abstract
Pathologically proven regional lymph node metastasis affects the prognosis in early stage oral cancer. Therefore we investigated invasive tumor patterns predicting nodal involvement and survival in patients with clinically node-negative T1 and T2 oral squamous cell carcinoma (cT1,2N0M0 OSCC). Ninety-one cases of cT1,2N0M0 OSCC treated with transoral resection of the primary tumor were assessed based on 3 types of invasive tumor patterns on histopathologic and pancytokeratin-stained immunohistological sections: the mode of invasion, worst pattern of invasion (WPOI), and tumor budding. The correlations among invasive tumor patterns, regional metastasis, and disease-free survival were analyzed. Of the 91 cases, 22 (24%) had pathologically proven regional metastasis. The mode of invasion (p<0.01) and tumor budding (p<0.01) were associated with regional metastasis as well as lymphovascular invasion (p = 0.04) in univariate analysis. In logistic regression analysis, however, tumor budding was the only independent predictor of regional metastasis (hazard ratio (HR) = 3.05, 95% confidence interval (CI) = 0.29–5.30, p<0.01). All three invasive patterns, the mode of invasion, WPOI, and tumor budding, were found to be significant predictors of 5-year disease-free survival (p<0.01, p = 0.03, and p<0.01, respectively) as well as lymphovascular invasion (p = 0.02) and perineural invasion (p = 0.02). A final model for Cox multivariate analysis identified the prognostic advantage of the intensity of tumor budding (HR = 2.19, 95% CI = 1.51–3.18, p<0.01) compared with the mode of invasion and WPOI in disease-free survival. Our results indicate that the intensity of tumor budding may be a novel diagnostic biomarker, as well as a therapeutic tool, for regional metastasis in patients with cT1,2N0M0 OSCC. If the pancytokeratin-based immunohistochemical features of more than five buds, and a grade 4C or 4D mode of invasion are identified, careful wait-and-see follow-up in a short period with the use of imaging modalities is desirable. If there are more than ten buds, a grade 4D mode of invasion, or WPOI-5 in the same section, wide resection of the primary tumor with elective neck dissection should be recommended.
Highlights
Oral squamous cell carcinomas (OSCC) constitute a broad range of tumors with diverse etiologies, the estimated age-standardized rate is relatively large, at 2.7 per 100,000 (3.7 for men and 1.8 for women) in 2012 [1]
The study consisted of 91 patients with cT1,2N0M0 oral squamous cell carcinomas (OSCC) treated with transoral resection of the primary tumor
The current retrospective study showed four interesting results. It showed that higher intensities of tumor budding and grade 4C and grade 4D modes of invasion were correlated with regional metastasis in patients with cT1,2N0M0 OSCC
Summary
Oral squamous cell carcinomas (OSCC) constitute a broad range of tumors with diverse etiologies, the estimated age-standardized rate is relatively large, at 2.7 per 100,000 (3.7 for men and 1.8 for women) in 2012 [1]. Despite recent advances in the clinical evaluation of regional metastasis in early stage OSCC, including imaging techniques such as computed tomography (CT) scanning, magnetic resonance imaging (MRI), ultrasonography (US), positron-emission tomography (PET)-CT, and serum tumor markers, it cannot always be determined. Despite this high risk of occult disease, the issue of whether to recommend elective neck dissection for patients with clinically node-negative disease represents an area of historic controversy. A recent prospective randomized controlled trial revealed that elective neck dissection resulted in higher rates of overall survival and disease-free survival than did therapeutic neck dissection for clinically node-negative T1 and T2 (cT1,2N0M0) OSCC [3]. The trial results mean that 8 patients would need to be treated with elective neck dissection to prevent one death, and four patients would need to be treated to prevent one nodal relapse (the development of nodal disease after the excision of the primary tumor in patients without elective neck dissection) as pointed out by the authors
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