Tumor Budding as a Histologic Prognostic Parameter in Oral Squamous Cell Carcinoma: Comparison of Scoring Systems and Rationale for the Use of Immunohistochemistry.

Abstract

Tumor budding (TB) is associated with nodal metastasis and worse outcomes in oral squamous cell carcinoma. However, there is a need for standardization of its assessment. To perform TB scoring using 2-tiered and 3-tiered systems, with and without pancytokeratin (CK) immunohistochemistry, and assess relationship with outcome parameters. Tumor buds were scored by using 2-tiered (low: <5; high: ≥5) and 3-tiered (low: 0-4; intermediate: 5-9; high: ≥10) systems on hematoxylin-eosin- and CK-stained sections. TB was evaluated in 400 oral squamous cell carcinomas, which were predominantly gingivobuccal (242; 61%), had aggressive worst patterns of invasion (WPOI) (WPOI-4: 59%; WPOI-5: 27%), and were late stage (298; 75%). Two-year disease-free survival (DFS) was 56.3%, and 2-year overall survival (OS) was 58.7%. Using 3-tiered scoring, 220 cases (55%) had low, 101 (25%) had intermediate, and 79 (20%) had high TB. With 2-tiered scoring, 220 cases (55%) had low and 180 (45%) had high TB. Greater concordance was seen between hematoxylin-eosin- and CK-stained sections with 2-tiered scoring: 14% were up-scored versus 25% with 3-tiered scoring. Cases with high and intermediate TB had significantly shorter DFS and OS. TB on CK-stained sections scored by both systems was an independent predictor of nodal metastasis. With all 4 scoring models, high TB was an independent predictor of recurrence. All 4 models showed similar predictive values for OS and DFS. TB is a significant predictor of nodal metastasis and recurrence, irrespective of site and stage. Three-tiered scoring does not show improved prediction of outcomes over 2-tiered scoring.