Tumor angiogenesis and metastasis: correlation in invasive renal cell carcinoma.

BACKGROUND: Experience suggests that tumor growth is dependent on angiogenesis. The intensity of angiogenesis in human cancer is reported to be predictive of the probability of metastasis in many types of cancer. The aims of this study were 1) to determine the relationship of microvessel density (MVD) in renal cell carcinoma to pathologic stage, and 2) to evaluate the role of MVD in metastasis. METHODS: Paraffin-embedded tumor specimens were reviewed from 34 unselected patients with RCC who had undergone surgery from 1986 to 1990 at Taichung Veterans General Hospital. The pathology findings and clinical records were reviewed to note relationships between pathologic stage and whether or not metastasis had occurred. Specimens were studied from 16 cases (eight Stage I cancers, five Stage II and three Stage III) without metastasis and from 18 cases (two Stage I, six Stage II, six Stage III and four Stage IV) in which metastasis later developed. Microvessels were highlighted by immunostaining endothelial cells for factor VIII-related antigen. Microvessels were counted in a x-400 field (0.1885 mm2/field) in the most active areas of neovascularization. RESULTS: The 16 patients without metastasis have survived for between 65 and 136 months (mean, 94.5 months), up to the present time. Of the 18 patients with metastasis, 15 died and three survived, with mean survivals of 42.8 months (range, 12-99 months). Mean overall MVD was 99.6 vessels; mean MVD was 98.5, 96.2, 109.3 and 90.0 in Stages I, II, III and IV tumors, respectively. Mean MVD was 99.3 in patients without metastasis and 99.9 in patients with metastasis. CONCLUSIONS: MVD does not correlate with pathologic stage and is of no prognostic significance in renal cell carcinoma.

Intracellular glutathione content of urothelial cancer in correlation to chemotherapy response.

We evaluated the possible correlation between intracellular glutathione (GSH) and drug sensitivity of urothelial cancer. Tissue GSH content of surgical specimens from 20 patients with urothelial cancer was assayed with high performance liquid chromatography (HPLC). GSH levels of cancer tissue (7.887 +/- 6.176 microM/mg protein) were significantly higher than GSH levels of normal mucosa (1.345 +/- 1.252 microM/mg). All patients having measurable lesions were then treated with methotrexate, epirubicin and cisplatin (MEC). These patients were classified into three groups according to clinical response criteria. GSH content in cancer tissue from four patients with complete response was 0.804 +/- 1.183 microM/mg protein. However, the cancer cells from patients with partial response and non-response contained a significantly higher level of GSH (6.295 +/- 2.459 (n = 8) and 12.955 +/- 6.141 microM/mg protein (n = 8), respectively). Intracellular glutathione content may play an important role in intrinsic resistance of urothelial cancer to MEC chemotherapy. It might be potentially used to predict drug sensitivity in urothelial cancer patients before starting chemotherapy.