Prognostic relevance of histologic grading, the cell cycle-associated antigen Ki-S1 and cell cycle regulators in malignant fibrous histiocytomas: a multivariate analysis.
The main aim of this study was to compare the prognostic impact of different histologic grading systems, the expression of the cell cycle-associated antigen DNA-topoisomerase-II-alpha (Ki-S1) and the expression of cell cycle regulators in malignant fibrous histiocytomas (MFH) using multivariate analyses. Paraffin-embedded tissue of 161 cases of MFH were studied immunohistochemically for the expression of the proliferation marker Ki-S1, cell cycle regulators (p53, MDM2, waf-1, pRb, p16) and the oncoprotein EGFR. The percentage of immunolabelled tumor cells (index) was assessed. The histologic grade was determined by the two-level grading systems of Costa, Tsujimoto and Pezzi, by the three-level grading systems of Coindre and Van Unnik and by the grading system presented here. Univariate analyses using the LOG rank test showed that all of the applied grading systems produce highly significant differences in survival between the grades of malignancy. Multivariate analyses with COX regression demonstrated that only the grading system presented here, based on the parameters necroses, mitoses and cellularity, had independent prognostic relevance. Moreover, the inclusion of the proposed grading system, the Ki-S1-index and a prognostic index primarily based on the expression of cell cycle regulators into the COX regression was suited for predicting survival in MFH. The grading system presented shows considerable advantages over the grading systems compared in this study for use in the routine pathology of MFH. The prognostic power of the proposed grading system can be enhanced by the combined study of cell cycle regulators and Ki-S1.
Brinck
U
U
Institute of Pathology, University of Göttingen, Germany.
Cordon-Cardo
C
C
Korabiowska
M
M
Kellner
S
S
Trybus-Galuszka
H
H
Stachura
J
J
Parwaresch
M R
MR
Schauer
A
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002453:Cell Cycle; D002648:Child; D002675:Child, Preschool; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D018219:Histiocytoma, Benign Fibrous / Q000401:mortality / Q000473:pathology*; D006801:Humans; D017730:Ki-1 Antigen / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009687:Nuclear Proteins; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis; D051736:Proto-Oncogene Proteins c-mdm2; D016160:Retinoblastoma Protein / Q000032:analysis; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D017730:Ki-1 Antigen; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D066246:ErbB Receptors