J Korean Med Sci.  2007 Sep;22(Suppl):S109-S114. 10.3346/jkms.2007.22.S.S109.

The Expression of Thymidine Phosphorylase in Cancer-infiltrating Inflammatory Cells in Stomach Cancer

• Jang JS
• Lee WS
• Lee JS
• Kim HW
• Ko GH
• Ha WS

• KMID: 1785798
• DOI: http://doi.org/10.3346/jkms.2007.22.S.S109

Abstract

Thymidine phosphorylase (TP) has shown to be up-regulated in several cancers and to play a role in angiogenesis and invasion. Most studies regarding TP have focused on cancer cells. Recently, evidences suggest that TP in cancer-infiltrating inflammatory cells (CIICs) also affect the cancer cell behavior. To evaluate the significance of TP expression of CIICs in gastric cancer, we assessed TP expression of cancer cells and CIICs separately using immunohistochemical assay on 116 paraffin-embedded tissue samples from stomach cancer patients and investigated their clinical significance. When subjects were divided into 4 groups according to the TP expression: cancer/matrix (+/+), C/M (+/-), C/M (-/+), and C/M (-/-), intratumoral microvessel density scores were higher in the C/M (+/-) group than in the C/M (-/-) group (p=0.02). For lymph node metastasis and survival, there were no significant differences among the 4 groups. However, there were significant differences in survival (p=0.035) and LN metastasis (p=0.023) between the two groups divided by TP expression of CIICs alone irrespective of TP expression of cancer cells. Taken together, this study suggested the TP expression in CIICs could affect lymph node metastasis and patients' survival in gastric cancer.

Keyword

Thymidine Phosphorylase; Inflammatory Cell; Matrix; Stomach Cancer

MeSH Terms

Adult
Aged
Female
Humans
Immunohistochemistry
Inflammation/*enzymology/pathology
Kaplan-Meiers Estimate
Lymphatic Metastasis
Lymphocytes, Tumor-Infiltrating/*enzymology/pathology
Male
Microcirculation/pathology
Middle Aged
Neovascularization, Pathologic
Prognosis
Stomach Neoplasms/blood supply/*enzymology/mortality/pathology
Thymidine Phosphorylase/*metabolism

Figure

• 

  Fig. 1 Immunohistochemical staining for thymidine phosphorylase (TP) in a gastric cancer specimen using antibody against TP. TP expression was heterogeneously identified in nucleus and/or cytoplasm of cancer cells and cancer-infiltrating inflammatory cells. (A) Positive staining is observed in the cytoplasm and nucleus of cancer cells and CIICs, Cancer (+)/Matrix (+). (×200). (B) TP-reactivity is observed in the cytoplasm and nucleus of cancer cells and in less than 50% of CIICs, Cancer (+))/Matrix (-). (×200). (C) Note that most TP-positive cells were CIICs, Cancer (-)/CIICs (+). (×200). (D) TP-reactivity is observed in less than 50% of CIICs and less than 5% Cancer cells Cancer (-)/Matrix (-). (×400).

• 

  Fig. 2 Relationship between IMVD and TP expression. The statistical difference was found between cancer (-)/matrix (+) and cancer (-)/matrix (-) (p=0.02).

• 

  Fig. 3 Relationship between lymph node metastasis and TP expression. (A) No statistical difference in lymph node metastasis was shown among 4 groups according to TP expression. (B) The patients with positive TP expression in CIICs showed more lymph node metastasis in two groups divided by TP reactivity in CIIC (p=0.019).

• 

  Fig. 4 The Kaplan-Meier curves for survival according to the TP expression patterns. (A) The patients were divided into 4 groups according to TP expression. This graph shows a trend of survival differences among four groups, but these differences assessed by log-rank test did not reach a statistically significant value (p=0.089). (B) A clear survival difference was observed when the patients were divided into two groups as matrix-positive group and matrix-negative group regardless of TP reactivity of cancer cells (p=0.035).

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