Immunohistochemical analysis with multiple antibodies in search of prognostic markers for clear cell renal cell carcinoma.
OBJECTIVE
To simultaneously analyze multiple biologic markers to identify strong prognostic markers for disease-specific survival of patients with clear cell renal cell carcinoma (ccRCC).


METHODS
The expression of Ki-67, p53, bcl-2, cyclin-D1, caveolin-1, vascular endothelial growth factor, and HER-2 was evaluated in 119 paraffin-embedded ccRCC specimens using immunohistochemistry. The clinical significance of these markers in relation to disease-specific survival was analyzed.


RESULTS
On univariate analysis, high-level staining for Ki-67 (P <0.0001), p53 (P = 0.0029), vascular endothelial growth factor (P = 0.0062), and caveolin-1 (P = 0.0396) was associated with decreased survival, but high-level staining for bcl-2 (P <0.0001) and cyclin-D1 (P = 0.0002) was associated with increased survival. Only HER-2 expression was not related to survival (P = 0.1131). Multivariate analysis revealed the following independent predictors of disease-specific survival: expression of p53 (P = 0.0059) or bcl-2 (P = 0.0413) in all cases of ccRCC; expression of p53 (P = 0.0043) or bcl-2 (P = 0.0227) in cases of grade 1-2 disease; and expression of p53 (P = 0.0207) in cases with metastasis at surgery.


CONCLUSIONS
Of the seven markers reviewed, p53 and bcl-2 were strong prognostic factors in all cases and in cases of grade 1-2 ccRCC. Only p53 attained independent prognostic significance in metastatic ccRCC. This information could prove useful in selecting markers to predict for survival and plan therapy for patients with ccRCC.
Phuoc
Nguyen Ba
NB
Department of Urology, Gifu University Graduate School of Medicine, Gifu, Japan.
Ehara
Hidetoshi
H
Gotoh
Takahiro
T
Nakano
Masahiro
M
Yokoi
Shigeaki
S
Deguchi
Takashi
T
Hirose
Yoshinobu
Y
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000912:Antibodies, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D002292:Carcinoma, Renal Cell / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D019938:Cyclin D1 / Q000378:metabolism; D005260:Female; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D007680:Kidney Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009392:Nephrectomy / Q000379:methods; D011336:Probability; D011379:Prognosis; D016016:Proportional Hazards Models; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012189:Retrospective Studies; D018570:Risk Assessment; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D016019:Survival Analysis
D000912:Antibodies, Neoplasm; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D019938:Cyclin D1