Immunohistochemical expression of thymidylate synthase as a prognostic factor and as a chemotherapeutic efficacy index in patients with colorectal carcinoma.

BACKGROUND: We assessed the importance of Thymidylate Synthase (TS) expression as a prognostic factor and as an index of therapeutic efficacy in patients with colorectal carcinoma. PATIENTS AND METHODS: TS expression in 66 patients with colorectal carcinoma was immunohistochemically assessed using the anti-TS antibody. TS expression, TS activity, clinicopathological characteristics and survival were evaluated and the correlation among them was studied. RESULTS: The cases studied included 53 patients with low grade positive/negative and 13 patients with high grade positive TS expression. TS levels were 8.69 +/- 10.01 pmol/g and 14.82 +/- 11.38 pmol/g, respectively. There was not correlation between clinicopathological characteristics and TS expression. Considering TS expression, the 5-year survival rate was significantly better for the 75.5% of the patients with low grade positive/negative TS than for the 38.5% of the patients with high grade positive TS (p < 0.01). CONCLUSION: The immunohistochemical expression of TS should be further investigated as a prognostic factor of survival and as an index of chemotherapeutic efficacy in colorectal carcinoma.

[Thymidylate synthase activity after preoperative administration of 5-FU in patients with gastric or colorectal cancer].

Continuous intravenous injection of 5-FU was given at 300 mg/m2 to patients with gastric or colorectal cancer for consecutive 3 days preoperatively, and the relationships between the time until collection of samples (from final administration of 5-FU to excision of tissue samples) and total thymidylate synthase (TS total) activity, free thymidylate synthase (TS free) activity, thymidylate synthase inhibition rate (TSIR), thimidine kinase (TK) activity, and tissue 5-FU and FdUMP concentrations investigated. TS total was shown to gradually reduce with time, but the relationship between time and the other assay items could not be identified due to large variability in the data. TS total and TK also proved to be affected also by the sites at which the samples were collected, and exhibited significantly higher enzyme activity in tumor tissue than that in normal tissue.

Do the expression of CD44, apoptosis and thymidylate synthase inhibition rate correlate with the efficacy of chemotherapy in colorectal cancer?

BACKGROUND: Tegafur-uracil(UFT;TAIHO Pharmaceutical Co.Ltd, Tokyo, Japan) is commonly used to treat digestive cancers. However, the inhibitors of metastasis in this agent have not been fully examined. To investigate a cell adhesion molecule, CD44, which may very well contribute to the pathogenesis of metastasis, we examined the association of CD44 and the thymidylate synthase inhibition rate(TSIR) with prognosis, and examined the expression of apoptosis in patients who were administrated tegafur-uracil before surgery for colorectal cancer. MATERIALS AND METHODS: This study included 66 patients who underwent curative resection of colorectal cancer. In these patients, tegafur-uracil(600 mg) was orally administered every day for 3 to 7 days before surgery, and Tegafur-uracil (400 mg) was orally administered every day for 2 years after surgery. CD44 and apoptosis were detected immunohistochemically and by the TUNNEL method, respectively. The TSIR was calculated from the total TS level, and free TS levels by modified Spears' method using fresh tumor tissue specimens. RESULTS: The TSIR of non-recurrent patients was significantly higher than that of recurrent patients(p < 0.05). The 5-year survival rate in CD44-low grade positive/negative patients (81.6%) was significantly higher than that in CD44-high grade positive patients (46.4%) (p < 0.005). The 5-year survival rate in apoptosis-high grade positive patients (89.7%) was significantly higher than that in apoptosis-low grade positive/negative patients(46.4%) (p < 0.001). With respect to the relationship between CD44 and apoptosis, the proportion of apoptosis-high grade positive patients among CD44-low grade positive/negative patients (55.3%) was significantly higher than that among CD44-high grade positive patients(28.6%) (p < 0.05). In the multivariate analysis, the CD44 expression was suggestive of an independent prognostic factor. CONCLUSION: Based on our results for TSIR, Tegafur-uracil may induce apoptosis of tumor cells in patients by the inhibition of thymidylate synthase. It was suggested that CD44 expression could be used as a possible independent predictor of survival. In addition, it was suggested that UFT, via the inhibition of CD44 expression caused the inhibition of distant metastasis.

An evaluation of malignancy and prognostic factors based on mode of lymph node metastasis in esophageal carcinoma.

This study was conducted to evaluate lymph node metastasis as a key prognostic factor in esophageal cancer. Metastatic lesions in lymph nodes were grouped by histological morphology as intracapsular or extracapsular, and the significance of lymph node metastasis was evaluated by relating metastatic lesions to clinical pathologic factors and patient prognosis. In our hospital, 46 of 81 patients who underwent resection of esophageal cancer developed lymph node metastasis. These 46 patients were enrolled in a study analyzing the relationship between the metastatic mode and the clinicopathological factors. The frequency of extracapsular metastasis was significantly high in patients with a profound depth of cancer, three or more metastases, distant metastasis (n3 and n4), or severe lymphatic invasion. The prognosis was significantly worse in patients with extracapsular metastasis, and this tendency was also seen even in patients with three or more metastases, limited metastasis (n1 and n2), or mild lymphatic invasion (ly0 and ly1). These findings suggest that the metastatic mode reflects the degree of esophageal cancer progression and is an important prognostic factor.