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. 2023 Sep;14(25):2608-2617.
doi: 10.1111/1759-7714.15043. Epub 2023 Jul 19.

Tumor budding and tumor-infiltrating lymphocytes can predict prognosis in pT1b esophageal squamous cell carcinoma

Zhuo Li  1 , Linxiu Liu  1 , Bingzhi Wang  1 , Jianming Ying  1 , Jie He  2 , Liyan Xue  1
Affiliations

Tumor budding and tumor-infiltrating lymphocytes can predict prognosis in pT1b esophageal squamous cell carcinoma

Zhuo Li et al. Thorac Cancer. 2023 Sep.

Abstract

Background: Tumor budding (TB) and tumor-infiltrating lymphocyte (TIL) are significant predictive indicators of lymph node metastasis (LNM) and unfavorable prognosis in various tumors. Currently, there is no gold standard for TB and TIL evaluation in esophageal squamous cell carcinoma (ESCC). This study aimed to identify the standard of TB and TIL evaluations and build a predictive model for prognosis among patients with pT1b ESCC.

Methods: We retrospectively analyzed the prognostic values of TB and TIL in 150 pT1b ESCC cases. Hematoxylin and eosin (H&E) and immunohistochemistry (IHC) of anti-pan cytokeratin (AE1/AE3) were used to analyze the threshold of TB, and intratumoral TIL and peritumoral TIL (pTIL) were evaluated using the receiver operating characteristic curves (ROC).

Results: We found that TB in a three-tiered grading system (low-TB: 0-4; middle-TB: 5-15; high-TB: ≥16) displayed an excellent prognosis prediction for LNM and survival based on IHC staining using a 20× objective lens. Low pTIL level (≤20%) was a significant indicator of LNM and unfavorable prognosis (p < 0.05). Moreover, lower tumor location and lymphovascular invasion (LVI) were correlated with an unfavorable prognosis (p < 0.05). A nomogram developed based on TB, pTIL, LVI, and tumor location showed good discrimination, as shown by the area under the ROC and calibration curves.

Conclusion: We therefore recommend identifying TB using a 20× objective lens under IHC staining and TIL adjacent to the tumor. Additionally, a nomogram was built for facilitating individualized prediction of survival for patients with pT1b ESCC.

Keywords: lymph node metastasis; nomogram; prognosis; tumor budding; tumor infiltrating lymphocyte.

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Conflict of interest statement

The authors confirm there are no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Receiver operating characteristic (ROC) curves of tumor budding for lymph node metastasis evaluated by hematoxylin & eosin (H&E) staining (a), and immunohistochemical (IHC) staining (anti‐pan cytokeratin, AE1/AE3) (b).
FIGURE 2
FIGURE 2
Survival curves for esophageal squamous cell carcinoma (ESCC) patients (N = 150) categorized by tumor budding according to X‐tile software. (a) The overall survival (OS) and (b) progression‐free survival (PFS) of ESCC patients.
FIGURE 3
FIGURE 3
Representative images of tumor budding (TB) activity of esophageal squamous cell carcinoma (ESCC) under a 20× objective lens by immunohistochemical (IHC) staining (anti‐pan cytokeratin, AE1/AE3). (a) ESCC with low grade tumor budding (TB) (0–4 TBs). (b) ESCC with middle grade TB (5–15 TBs). (c) ESCC with high grade TB (≥16 TBs).
FIGURE 4
FIGURE 4
Representative images of tumor infiltrating lymphocyte (TIL) level of esophageal squamous cell carcinoma (ESCC). (a) TIL comprise intratumoral TIL (iTIL, green area) and peritumoral TIL (pTIL, orange area). Magnified images of iTIL and pTIL are shown. (b) ESCC with low pTIL (≤20%). (c) ESCC with high pTIL (>20%). (d) ESCC with low iTIL (≤7%). (e) ESCC with high iTIL (>7%).
FIGURE 5
FIGURE 5
Tumor infiltrating lymphocyte (TIL). (a) Receiver operating characteristic (ROC) curves of TIL for lymph node metastasis. (b) The overall survival (OS) and (c) progression‐free survival (PFS) of patients with ESCC categorized by peritumoral TIL level.
FIGURE 6
FIGURE 6
A nomogram for predicting the probability of poor progression‐free survival in patients with pT1b esophageal squamous cell carcinoma.
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