Importance of Thymidine Phosphorylase Expression at the Invasive Front of T3 Rectal Cancer as a Prognostic Factor

Abstract

Purpose: Vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP) are angiogenic factors. We evaluated the relationship between the degree of expression of binary angiogenic factors and the malignant potential of colorectal cancer. Methods: This study was conducted in 61 patients with T3 rectal cancer who underwent surgical curative resection between 1998 and 2002. Paraffin-embedded sections of their surgical specimens were immunostained for VEGF and TP. The relationship between the expression level of binary angiogenic factors and lymph node metastasis was evaluated. Results: Expression of VEGF was present only in the tumor cells of all patients, and expression was absent in the stromal cells around the invasive front of the tumor. Expression of TP was mainly present in the stromal cells around the cancer nests or around the invasive margin of the cancer. There was no relationship between expression of TP in the stromal cells around the invasive front of the tumor and lymph node metastasis. However, there was a significant relationship between expression of TP at the invasive front of the tumor and lymph node metastasis (p = 0.014). Moreover, TP expression in the tumor cells was the only independent factor that correlated with the postoperative recurrence (p = 0.024) with an odds ratio of 11.973 by multivariate logistic regression analysis. Conclusion: Expression of TP at the invasive front of the tumor may be a useful indicator of the malignant potential of advanced rectal cancer.

Clinicopathological significance of vascular endothelial growth factor, thymidine phosphorylase and microvessel density in colorectal cancer

“…A high VEGF expression level is considered to be a prognostic factor of colorectal cancer, particularly in patients exhibiting lymph node metastasis. Previous studies have reported significant correlations between clinicopathologic features and TP expression levels ( 19 , 35 , 37 ), whereas other studies have reported an inverse correlation between the TP expression level and lymph node/hematogenous metastasis ( 22 ); thus, the association between TP expression level and clinicopathologic features is considered to be controversial ( 23 , 37 – 41 ). It was hypothesized in the current study that the significance of the TP expression levels is minimal with regard to angiogenesis (which is assessed by MVD), when high VEGF expression levels are sufficient to induce VEGF-associated angiogenesis.…”

“…Furthermore, various reports regarding colorectal cancer specified that VEGF expression was closely correlated with tumor angiogenesis ( 11 , 12 , 32 ), and may be considered an independent prognostic factor ( 1 , 7 , 33 ), while a study indicated that there was no apparent correlations ( 12 ). In addition, previous reports analyzed the positive correlations between a high VEGF expression level and lymph node metastasis ( 1 , 34 ), while certain studies revealed negative correlations ( 35 , 36 ). In the present study, MVD in the high VEGF expression group was observed to be significantly higher than that of the low VEGF expression group, and patients' overall survival rate in the high VEGF expression group tended to be lower when compared with that of the low VEGF expression group.…”

Using a Multivariable Model for Prediction and Diagnosis

“…Logistic regression analysis is used when the dependent variable is dichotomous or nominal, in which case the explanatory variables can be numerical, ordinal, or nominal. Multivariable logistic regression analysis has been widely used for prediction 1,2 and diagnosis 3 . References 1 and 2 are only two examples of recent studies dealing with colorectal cancer.…”