engleski

Relationship Between Renal Artery Changes, Tumor Necrosis and Expression of Vascular Endothelial Growth Factor (VEGF) in Renal Cell Carcinoma

Tumor necrosis in renal cell carcinoma (RCC) is found to be one of the independent prognostic factors, associated with decrease in microvessel density and an increase of VEGF protein expression, manly within the perinecrotic rim (1). Main renal artery may show different lesions such as arteriosclerosis or fibromuscular dysplasia (FMD) but connection between renal artery changes and other prognostic factors in RCC is still unknown (2, 3, 4, 5, 6). We analyzed a consecutive series of 55 patients (M:F=35:20) with RCC who underwent nephrectomy in the year 2003. Patients were aging from 35-79 years (mean 59.8) and the tumor size was 2.5-16 cm (mean 7.1). Tumor necrosis was found in 43 (78.2%) cases of RCC of which 32 had less than 50% tumor necrosis and 11 tumors contained more than 50% necrotic areas. Nuclear grade of RCC was determined according to Fuhrmann et al (7). Specimens were routinely fixed, embedded in paraffin, cut and stained with hematoxylin and eosin, Mallory trichrome method and orcein. Immunohistochemical analysis was performed using primary antibodies to VEGF (DAKO, Copenhagen, Denmark). Immunohistochemical reaction was assessed as: 0-no positive tumor cells ; 1-up to 10% positive tumor cells ; 2->10-50% positive tumor cells ; 3-more than 50% positive tumor cells. Renal arteries of 23 (41.8%) patients (M: F=18:5) showed no changes (Group I). These patients were in age from 38-78 years (mean 58.7) and tumors measured from 2.5-17 cm (mean 7.4). FMD (Group II) was found in 25 (45.5%) patients (M:F=12:13) ranging in age from 35-79 years (mean 59.1), and the tumor size was 3-16 cm (mean 8.2). Atherosclerotic changes of renal arteries (Group III) were observed in 7 (12.7%) patients (M:F=5:2), aged from 60-69 years (mean 62.0) with tumors from 2.5-14 cm (mean 6.4). VEGF expression was negative (0-no positive tumor cells) in 14 cases, 19 cases had less than 10% positive tumor cells, 13 cases had 10-50% positive tumor cells and 9 tumors expressed VEGF in more than 50% tumor cells. Statistical analysis did not show significant difference in age, tumor size or nuclear grade between the three groups regarding renal artery status. However, tumors without renal artery changes were more frequently without necrotic areas (7/12), in comparison with other groups, but those tumors also showed higher VEGF expression in tumors cells (only 2/23 cases without renal artery changes showed negative reaction for VEGF expression). Tumors with FMD usually contained necrotic areas (22/25 cases), but they also had the highest number of negative tumor cells expression for VEGF (9/14 tumors with negative VEGF expression were tumors with FMD). Renal artery changes are very common in patients with RCC (8, 9). Tumor necrosis was more common in patients with associated FMD and atherosclerotic changes of renal arteries. However, although it would be expected that tumors with more necrotic areas produce VEGF protein, the VEGF expression in this group was more frequently negative. The cause of renal artery changes and their relationship to the degree of tumor necrosis and other VEGF expression in tumor cells should be further analyzed.

renal artery changes; tumor necrosis; VEGF; renal cell carcinoma

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