Fig 1.
Representative photographs of classification of mode of invasion (H&E staining, immunohistochemical pancytokeratin staining, x40 magnification).
(1A,1B) grade 1, (1C,1D) grade 2, (1E,1F) grade 3, (1G,1H) grade 4C, and (1I,1J) grade 4D.
Fig 2.
Representative photographs of classification of worst pattern of invasion (H&E staining, immunohistochemical pancytokeratin staining, x200 magnification).
(2A,2B) Worst pattern of invasion (WPOI)-1, (2C,2D) WPOI-2, (2E,2F) WPOI-3, (2G,2H) WPOI-4, and (2I,2J, x40 magnification) WPOI-5.
Fig 3.
Representative photographs of intensity of tumor budding (immunohistochemical pancytokeratin staining, x200 magnification).
(3A) Low intensity of tumor budding (<5 buds), (3B) intermediate intensity of tumor budding (≥5~<10 buds), and (3C) high intensity of tumor budding (≥10 buds).
Fig 4.
Photographs of immunohistochemical pancytokeratin staining show representative examples of grade 4D mode of invasion and worst pattern of invasion (WPOI)-4 at x40 magnification.
The region in the rectangle is shown at x200 magnification in the lower panel, which shows 12 buds.
Fig 5.
Photographs of immunohistochemical pancytokeratin staining show representative examples of grade 3 mode of invasion and WPOI-5 at x12.5 magnification.
The yellow line measures a distance >1 mm between the main tumor and the next focus of dispersed islands. The region in the rectangle is shown at x200 magnification in the lower panel, which shows 1 bud.
Fig 6.
Kaplan-Meier survival curves by mode of invasion (A), worst pattern of invasion (WPOI) (B), tumor budding (C), lymphovascular invasion (D), and perineural invasion (E).
5-year disease-free survivals were 58.0% for grade 1+2+3 mode of invasion, 36.4% for grade 4C mode of invasion, 0.0% for grade 4D mode of invasion (A), 58.4% for WPOI-1+2+3+4, 33.3% for WPOI-5, 65.0% for low-intensity tumor budding (<5 buds), 37.5% for intermediate-intensity tumor budding (≥5 buds-<10 buds), 23.1% for high-intensity tumor budding (≥10 buds), 58.1% for absence of lymphovascular invasion, 33.3% for presence of lymphovascular invasion, 56.1% for absence of perineural invasion, and 20.0% for presence of perineural invsion in patients with clinically node-negative T1 and T2 oral squamous cell carcinoma.
Fig 7.
Kaplan-Meier curves of disease-free survival (DFS) in patients in combined groups with the intensity of tumor budding and mode of invasion (A) or worst pattern of invasion (WPOI) (B).
In group A, the 5-year DFSs were 70.4% with low tumor budding and grade 1+2+3 mode of invasion ①, 66.7% with low tumor budding and grade 4C mode of invasion ②, 50.0% with intermediate tumor budding and grade 1+2+3 mode of invasion ③, 0% with intermediate tumor budding and grade 4C mode of invasion ④, 20.0% with high tumor budding and grade 1+2+3 mode of invasion ⑤, 33.3% with high tumor budding and grade 4C mode of invasion ⑥, and 0% with high tumor budding and grade 4D mode of invasion ⑦. In group B, the 5-year DFSs were 72.8% with low tumor budding and WPOI-1+2+3+4 ①, 44.4% with low tumor budding and WPOI-5 ②, 36.4% with intermediate tumor budding and WPOI-1+2+3+4 ③, 60.0% with intermediate tumor budding and WPOI-5 ④, 33.3% with high tumor budding and WPOI-1+2+3+4 ⑤, and 0% for high tumor budding and WPOI-5 ⑥.