Prognostic Role of Tumor‐Infiltrating Lymphocytes and Tumor Budding in Early Oral Tongue Carcinoma

Abstract

Objectives/Hypothesis Occult lymph metastasis is an important prognosticator for the treatment of early oral tongue squamous cell carcinoma (SCC). The objective of this study was to evaluate the prognostic significance of tumor‐infiltrating lymphocytes (TILs) in early oral tongue SCC. The combination of the TIL subtype and intermediate‐ or high‐grade budding scores was investigated as a prognostic marker for occult neck metastases. Study Design Retrospective study. Methods Specimens from 62 patients with early oral tongue SCC treated with only primary surgery were analyzed by immunohistochemistry for CD4+, CD8+, FoxP3+, and CD45RO+ T cells and CD163+ macrophages. The highest number of each TIL subtype was counted in two areas of parenchyma and stroma in the tumor (Tumor) and peripheral stroma of the invasion margin. Results Based on multivariate analysis, a high density of Tumor CD163+ macrophages served as the poorest prognostic factor for regional control (RC) and disease‐free survival (DFS). Patients with both a high density of Tumor CD163+ macrophages and an intermediate‐ or a high‐grade budding score had a poor prognosis for RC according to the log‐rank test. Conclusions In summary, each TIL subtype may use different mechanisms during early and advanced stages of oral tongue SCC. A high density of Tumor CD163+ macrophages was determined to be a risk factor for RC and DFS as well as an additional stratification factor for RC in patients with intermediate‐ or high‐grade budding scores. Therefore, identifying TIL subtypes in daily clinical practice can help determine a more successful and individualized therapeutic approach for early oral tongue SCC. Level of Evidence Step 4 (Level 4) Laryngoscope, 131:2512–2518, 2021

The Emerging Impact of Tumor Budding in Oral Squamous Cell Carcinoma: Main Issues and Clinical Relevance of a New Prognostic Marker

“…Double cut-off: 0 and 5 buds/field [ 68 , 72 ] 3 and 5 buds/field [ 18 ] 5 and 10 buds/field [ 28 , 29 , 36 , 64 , 65 , 73 ] …”

“…n. of HPF evaluated: 1, 5, 10 1 [ 5 , 15 , 16 , 18 , 19 , 23 , 24 , 25 , 26 , 28 , 29 , 30 , 32 , 34 , 36 , 37 , 38 , 40 , 43 , 44 , 53 , 54 , 55 , 56 , 57 , 60 , 61 , 62 , 63 , 64 , 65 , 67 , 68 , 69 , 71 , 73 , 74 ] 5 [ 15 , 33 ] 10 [ 19 , 24 , 66 …”

“…1 [ 5 , 15 , 16 , 18 , 19 , 23 , 24 , 25 , 26 , 28 , 29 , 30 , 32 , 34 , 36 , 37 , 38 , 40 , 43 , 44 , 53 , 54 , 55 , 56 , 57 , 60 , 61 , 62 , 63 , 64 , 65 , 67 , 68 , 69 , 71 , 73 , 74 ]…”

“…Magnification ×10 [ 62 ] ×20 [ 16 , 17 , 18 , 23 , 25 , 26 , 28 , 29 , 30 , 32 , 34 , 36 , 37 , 38 , 40 , 43 , 44 , 53 , 54 , 55 , 57 , 58 , 59 , 60 , 61 , 63 , 64 , 68 , 69 , 70 , 71 , 73 , 74 ] ×25 [ 15 ] ×40 [ 24 , 25 , 31 , 66 ] …”

“…Currently, researchers have been focusing on the histological characteristics of the tumor microenvironment (TME) as a source of reliable markers for cancer progression. Accumulating evidence suggests TB as an independent prognostic factor in OSCC [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ] and in oral tongue squamous cell carcinoma (OTSCC), the most involved oral subsite [ 22 , 23 , 26 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ]. Nevertheless, due to several methodological shortcomings, the exact role of TB in OSCC is not yet elucidated, and conflicting results have been reported.…”