Primary apoptosis as a prognostic index for the classification of metastatic renal cell carcinoma.
OBJECTIVE
We identified novel biological markers of prognosis in primary histopathological specimens from patients with metastatic renal cell carcinoma.


METHODS
Apoptotic indexes (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling), proliferation rates (Ki-67 antigen), p21 (WAF1/cip1) expression and CD95 (APO-1/Fas) expression were determined in paraffin embedded nephrectomy specimens from 73 patients with histologically confirmed, progressive metastatic disease. Kaplan-Meier survival analysis, log rank statistics and 2-proportional Cox regression analysis were done to identify new risk factors in addition to conventional classification criteria, and demonstrate statistical independence.


RESULTS
Multivariate analysis indicated that primary tumor apoptosis (p = 0.0116) and the interval from diagnosis to metastatic disease (p = 0.002) had a high predictive impact on overall survival after initial diagnosis. Patients were assigned to 2 risk groups, namely a poor prognosis group with a median survival of 20 months, defined by apoptosis less than 6% in the primary tumor nephrectomy specimen and a time from initial diagnosis to metastatic disease of less than 6 months, and a good prognosis group with a median survival of 56 months, defined as the absence of 1 or 2 risk factors.


CONCLUSIONS
Our findings showed that primary tumor apoptosis is a novel independent predictor in patients with metastatic renal cell carcinoma at initial diagnosis. It leads to a new prognostic index in the pretreatment classification of metastatic renal cell carcinoma.
Richter
E N
EN
Hämatologie und Onkologie and Urologische Klinik, Medizinische Hochschule Hannover, Hannover, Germany.
Oevermann
K
K
Buentig
N
N
Storkel
S
S
Dallmann
I
I
Atzpodien
J
J
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000401:mortality / Q000473:pathology*; D002455:Cell Division / Q000502:physiology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000032:analysis; D007668:Kidney / Q000473:pathology; D007680:Kidney Neoplasms / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis; D019014:fas Receptor / Q000032:analysis
D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019394:Ki-67 Antigen; D019014:fas Receptor