Appraisal of intratumoral microvessel density, MIB‐1 score, DNA content, and p53 protein expression as prognostic indicators in patients with locally confined renal cell carcinoma

• Published in: Cancer 1997-11, Vol.80 (9), p.1768-1775
• Main Authors: Gelb, Arnold B., Sudilovsky, Daniel, Wu, C. Daniel, Weiss, Lawrence M., Medeiros, L. Jeffrey
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antigens, Nuclear; Biological and medical sciences; Biomarkers, Tumor - analysis; Carcinoma, Renal Cell - blood supply; Carcinoma, Renal Cell - diagnosis; Cell Division; DNA content; DNA, Neoplasm - metabolism; Female; Flow Cytometry; Follow-Up Studies; Humans; Immunohistochemistry; intratumoral microvessel density; Ki-67 Antigen; Kidney; Kidney Neoplasms - blood supply; Kidney Neoplasms - diagnosis; Kidneys; Male; Medical sciences; MIB‐1; Middle Aged; Multivariate Analysis; Neovascularization, Pathologic; Nephrology. Urinary tract diseases; Nuclear Proteins - analysis; p53; Ploidies; Prognosis; renal cell carcinoma; S Phase; Survival Analysis; S‐phase fraction; Tumor Suppressor Protein p53 - metabolism; Tumors of the urinary system
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/(SICI)1097-0142(19971101)80:9<1768::AID-CNCR11>3.0.CO;2-3

BACKGROUND The prognostic values of intratumoral microvessel density (iMVD), tumor cell proliferation rate, DNA content (ploidy), and p53 protein expression are controversial or have not been well studied in patients with renal cell carcinoma (RCC) confined to the kidney. METHODS A uniform group of 52 clear cell (conventional) RCCs confined to the kidney (classified as T1N0M0 or T2N0M0) were analyzed for iMVD, MIB‐1 score, DNA content, S‐phase fraction, and p53 protein expression by immunohistochemical methods or flow cytometry. iMVD was evaluated in a single area (X200, 1.15 mm2) representative of the highest MVD (neovascular "hot spot") after independently highlighting endothelial cells with antibodies specific for factor VIII‐related antigen (F8/86) and CD31 (JC/70A). The MIB‐1 antibody (Ki‐67 antigen) score was used as a marker for the tumor cell proliferation rate. DNA content and S‐phase fraction were determined by flow cytometry using paraffin embedded tissue. p53 expression was assessed using the D07 antibody. RESULTS The median time of clinical follow‐up was > 9 years. Eleven patients died of disease; the median time to death was 26 months. iMVD counts using antifactor VIII and anti‐CD31 were tightly correlated (correlation coefficient = 0.89). S‐phase fraction was higher in aneuploid tumors than in diploid tumors (mean, 12.4% vs. 4.3%; P = 0.01). Using univariate survival analyses, tumor size (stage classification pT1 vs. PT2; P = 0.01) and nuclear grade (P = 0.04) were associated with shortened survival. No statistically significant differences in survival were found for iMVD, MIB‐1 score, DNA content, S‐phase fraction, or p53 expression. Only two cases strongly expressed p53 protein; both tumors were of high nuclear grade. Using multivariate survival analyses, nuclear grade and tumor size were the only independent prognostic factors (best model P = 0.002). CONCLUSIONS In this study, nuclear grade and tumor size were found to be independent predictors of survival in locally confined clear cell (conventional) RCC, as has been shown previously for locally confined RCC in general. MIB‐1 score, iMVD counts, DNA content, S‐phase fraction, and p53 expression did not contribute additional prognostic information. Cancer 1997; 80:1768‐75. © 1997 American Cancer Society. In a series of 52 clear cell renal cell carcinomas confined to the kidney (classified as pT1N0M0 or pT2N0M0), intratumoral microvessel density, MIB‐1 (Ki‐67) score, S‐phase fraction, DNA