Yonsei Med J.  2020 Apr;61(4):291-300. 10.3349/ymj.2020.61.4.291.

Yonsei Criteria, a Potential Linkage to Intratumoral Foxp3⁺/CD8⁺ Ratio for the Prediction of Oncologic Outcomes in Resected Left-Sided Pancreatic Cancer

• Hwang HK
• Lee SH
• Kim HI
• Kim SH
• Choi J
• Kang CM
• Lee WJ

• KMID: 2471914
• DOI: http://doi.org/10.3349/ymj.2020.61.4.291

Abstract

PURPOSE
This study sought to investigate associations among Yonsei criteria (tumor confined to the pancreas, intact fascia layer between the distal pancreas and the left adrenal gland and kidney, and tumor located more than 1-2 cm from the celiac axis) and tumor infiltrating lymphocytes in pancreatic cancer.
MATERIALS AND METHODS
Patients who underwent curative distal pancreatectomy due to left-sided pancreatic cancer from January 2000 to December 2011 were enrolled. Follow-up was completed September 30, 2015.
RESULTS
Fifty patients were enrolled. Having ≥ two metastatic lymph nodes (LNs, p=0.002), intraoperative transfusion (p=0.011), low levels of tumor infiltrating CD8⁺ T-cells (p=0.001), and a high Foxp3⁺/CD8⁺ ratio (p=0.009) were independent risk factors for disease-free survival. Not satisfying the Yonsei criteria (p=0.021), having ≥ two metastatic LNs (p=0.032), low levels of tumor infiltrating CD8⁺ T-cells (p=0.040) and a high Foxp3⁺/CD8⁺ ratio (p=0.032) were associated with unfavorable overall survival. High levels of CA19-9 and not satisfying the Yonsei criteria were significantly associated with a high Foxp3⁺/CD8⁺ ratio [Exp(β)=3.558; 95% confidence inverval: 1.000-12.658; p=0.050].
CONCLUSION
Yonsei criteria may be clinically detectable biologic marker with which to predict immunologic status and survival in pancreatic cancer patients.

Keyword

Pancreatic cancer; tumor infiltrating lymphocyte; cytotoxic T lymphocyte; regulatory T lymphocyte

MeSH Terms

Adrenal Glands
Biomarkers
Disease-Free Survival
Fascia
Follow-Up Studies
Humans
Kidney
Lymph Nodes
Lymphocytes, Tumor-Infiltrating
Pancreas
Pancreatectomy
Pancreatic Neoplasms*
Risk Factors
T-Lymphocytes
Biomarkers

Figure

• 

  Fig. 1 Hematoxylin and eosin, and IHC staining for tumor-infiltrating T lymphocytes. Hematoxylin and eosin staining from paraffin blocks (A) was performed to confirm tissue quality. IHC detection of CD3+ T lymphocytes (B), CD4+ helper T lymphocytes (C), CD8+ cytotoxic T lymphocytes (D), Foxp3+ regulatory T lymphocytes (E), and granzyme B+ activated cytotoxic T lymphocytes (F) in consecutive sections is shown (original magnification, ×400). IHC, immunohistochemical.

• 

  Fig. 2 Kaplan-Meier analysis of DFS (A) and OS (B) according to CD8+ levels (low vs. high; number of cells stained with immunohistochemical staining). The group with high levels of CD8+ showed favorable survival outcomes in regards to DFS (p=0.001) and OS (p=0.040). DFS, disease-free survival; OS, overall survival.

• 

  Fig. 3 Kaplan-Meier analysis of DFS (A) and OS (B) according to Foxp3+/CD8+ ratio (low vs. high). Low Foxp3+/CD8+ ratio showed favorable survival outcomes in regards to DFS (p=0.009) and OS (p=0.032). Foxp3, forkhead/winged helix transcription factor. DFS, disease-free survival; OS, overall survival.

• 

  Fig. 4 Kaplan-Meier analysis of DFS (A) and OS (B) according to the Yonsei criteria. Satisfaction of the Yonsei criteria indicated favorable survival outcomes in regards to DFS (p=0.021) and OS (p=0.001). DFS, disease-free survival; OS, overall survival.

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