p53, bcl-2 and thymidine phosphorylase as predictive markers of chemotherapy in patients with advanced and recurrent gastric cancer.

PURPOSE: To study the relationship between expression of p53, bcl-2, thymidine phosphorylase and Ki-67 and the response to chemotherapy and survival in patients with recurrent and advanced gastric cancer. MATERIALS AND METHODS: Protein expression was assessed immunohistochemically in 28 patients treated with 5-fluorouracil, pirarubicin and cisplatin (FAP). RESULTS: The response rate in patients positive for p53 expression was 23% compared with 47% of p53-negative patients. The response rate was also reduced from 44% in patients negative for bcl-2 protein expression to 25% in bcl-2 positive patients. Thymidine phosphorylase (dThdPase) expression was observed in 20 patients (71%), 50% of whom responded to chemotherapy, while patients negative for dThdPase expression did not respond to chemotherapy. The correlation between response rate and dThdPase-positivity was statistically significant (p < 0.05). However, with regard to patient survival, p53- and bcl-2-negative patients showed significantly better survival than patients positive for p53 and/or bcl-2 (p = 0.036). CONCLUSION: While dThdPase expression may be a useful predictor of response to chemotherapies that include 5-FU, p53 and bcl-2 expression may predict the outcome of patients with recurrent and advanced gastric cancer following chemotherapy.

Thymidine phosphorylase expression in gastric cancer in association with proliferative activity and angiogenesis.

BACKGROUND: Thymidine phosphorylase (dThdPase) has been reported to stimulate angiogenesis in vivo. We investigated dThdPase expression in gastric cancer in association with angiogenesis and proliferative activity. MATERIALS AND METHODS: One hundred and forty-eight gastric cancer patients who had received radical gastrectomy were investigated. RESULTS: Positive dThdPase staining was observed in 98 cases. The microvessel counts for positive and negative cases were 44.1 and 29.6, respectively, representing a significant correlation. The mean PCNA index of positive cases was significantly higher than that of negative cases. The patients with positive dThdPase staining in high intensity displayed decreased post-operative survival compared to those without. CONCLUSION: Our results suggest that proliferative activity of gastric cancer is related to dThdPase expression and angiogenesis and that dThdPase expression is associated with angiogenesis. dThdPase expression could also be a prognostic factor for gastric cancer patients.

[A case of surgical resection for metachronous multiple liver metastases of chromophobe cell renal carcinoma].

A 64-year-old female was hospitalized because of multiple liver metastasis, during the postoperative observation of chromophobe cell renal carcinoma. Injection of Epirubicin/Lipodol into the right hepatic artery followed by transcatheter arterial embolization was performed two times, and the metastatic foci responded favorably to this therapy. Since no new metastatic tumors were observed in the liver nor any other organs, a partial hepatectomy was thus performed. The liver tumor was pathologically diagnosed to be metastasis of the chromophobe cell renal carcinoma. The postoperative course has been uneventful and at present, 6 months after the operation, no further tumors have been observed.

Phase II study of 5-fluorouracil, pirarubicin and low-dose consecutive administration of cisplatin for advanced and recurrent gastric cancer.

BACKGROUND: The FAP regimen was modified and low-dose consecutive daily administration of cisplatin (CDDP) and continuous infusion of 5-fluorouracil (5-FU) and pirarubicin were employed to reduce the toxicity and achieve synergy. Patients with advanced and recurrent gastric cancer were treated with this regimen as early phase II trial and its efficacy and toxicity were assessed. METHODS: Twenty-nine patients with advanced or recurrent gastric cancer were treated with intravenous 5-FU, 360 mg/m2, continuous infusion, on days 1-5 and 8-12, CDDP, 10 mg/body, drip infusion, on days 1-5 and 8-12 and pirarubicin, 20 mg/body, on days 1 and 8, which was repeated every 4 weeks. RESULTS: One complete (CR) and 10 partial (PR) responses were observed. Eleven patients showed no change (NC) and seven had progressive disease (PD). The overall response rate (CR and PR) was 37.9%. The response rates of lymph node metastatic lesions and primary gastric lesions were 47 and 44%, respectively. The major toxicity was bone marrow suppression, which was well tolerated. Grade 3/4 nausea/vomiting did not occur. The median survival of all patients was 30 weeks, that of those who responded was 48 weeks and that of those showing NC or PD was 24 weeks. CONCLUSIONS: This modified FAP regimen was considered useful with a moderate response and less severe toxicity, but further investigation is necessary.

Ki-67 antigen expression in relation to clinicopathological variables and prognosis in gastric cancer.

One hundred and thirty surgical specimens of gastric adenocarcinoma were obtained from patients who had undergone radical gastrectomy. The samples were formalin-fixed, paraffin-embedded and used for immunostaining of Ki-67 antigen. Mean Ki-67 index was 41.8% (SD 15. 7%, range 8.2-84.2%). Differentiated carcinomas had a higher Ki-67 index than undifferentiated tumors, although other clinicopathological variables, including lymph node metastasis and depth of invasion showed no correlation with Ki-67 index. In the undifferentiated tumors, Ki-67 index correlated with lymph node involvement. A high Ki-67 index ( 55%) was found to be an independent indicator of poor prognosis in patients with undifferentiated tumors.

The relationship between the expression of proliferating cell nuclear antigen and clinicopathological variables of gastric-cancer.

A monoclonal antibody against proliferating cell nuclear antigen (PCNA), PC10, was applied to 96 gastrectomy specimens obtained from patients with gastric cancer. Resected tissue was routinely processed and stained immunohistochemically with PC10. One thousand tumor cells were counted and the ratio of the number of stained cells to total tumor cells was calculated as the PCNA index, which ranged from 13.8% to 88.8% with a mean of 61.4%. Although the PCNA index did not correlate with pathological variables including histological type, lymph node metastasis, growth pattern and venous invasion, it was significantly lower in mucosal carcinomas compared with submucosal and advanced carcinomas.

Chromosome changes in desmoid tumors developed in patients with familial adenomatous polyposis.

Chromosome analyses were performed on benign desmoid tumors obtained from two female patients with familial adenomatous polyposis (FAP), one of whom was diagnosed as having Gardner syndrome (GS). The modal chromosome number was 46 in both specimens, and detailed Q-banding analysis in Case 1 (GS) revealed a clonal abnormality of an interstitial deletion of the long arm of chromosome 5, del(5)(q21q31). The deleted region included an assigned locus for an FAP major gene (5q21-q22). All of the metaphases analyzed in this case showed an extra segment of bright fluorescence on the short arm of chromosome 15, but this unusual chromosome (15p+) was observed in both peripheral lymphocyte and skin fibroblast cultures from the patient, indicating that the 15p+ was constitutional in nature. In Case 2, no clonal rearrangements were identified and most cells had a normal karyotype. However, two cells showed rearrangements involving a 17q with non-identical breakpoints, one of which was observed as a solitary chromosome change. Based on the present findings in Case 1 and those reported so far, the chromosomal defect on 5q might be one of the causal genetic events primarily associated with the development of both benign desmoid tumors and colorectal adenomas and carcinomas in FAP patients.