Ki-S1--a prognostic marker for hypopharyngeal carcinoma with potential predictive value for response to chemotherapy.
BACKGROUND
It has previously been shown that the proliferative activity, determined by means of the monoclonal antibody Ki-S11 against the Ki-67 protein, is a significant prognostic factor for squamous cell carcinoma of the hypopharynx (SCCH). We now investigated the prognostic and the predictive impact of Ki-S1, a monoclonal antibody which detects an epitope of topoisomerase II alpha, another proliferation-associated antigen.


METHODS
The proliferation index (PI) in terms of Ki-S1 immunolabeling was evaluated on tumor specimens from 131 patients with SCCH. Survival probabilities over an observation time of 72 months were calculated by Kaplan-Meier analysis.


RESULTS
Patients with low PI (< or = 45%) had a significantly improved 5-year survival (33.2%) compared with patients with high PI (> 45%), of whom only 11% survived after 5 years (p = 0.001). Since there was no significant difference between the results obtained with Ki-S1 and Ki-S11, the present data confirm the prognostic significance of the proliferative activity in SCCH.


CONCLUSIONS
Topoisomerase II alpha is also the target of many antineoplastic drugs and it has been proposed that its expression in tumor cells correlates with chemosensitivity. The high average topoisomerase II alpha content in SCCH therefore promises a good responsiveness to topoisomerase inhibitors. Because Ki-S1 directly measures cellular topoisomerase II alpha expression, it might be exploited not only as a prognostic indicator but also as a predictive marker for patients with SCCH.
Kuropkat
Christiane
C
Department of Otorhinolaryngology, Head and Neck Surgery, University of Marburg, Deutschhausstr. 3, 35037 Marburg, Germany. kuropkat@post.med.uni-marburg.de
Rudolph
Pierre
P
Parwaresch
Reza
R
Werner
Jochen A
JA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D002455:Cell Division / Q000502:physiology; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D004268:DNA-Binding Proteins; D000939:Epitopes / Q000032:analysis / Q000276:immunology; D005260:Female; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000276:immunology / Q000378:metabolism*; D011237:Predictive Value of Tests
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D000939:Epitopes; D009687:Nuclear Proteins; D004250:DNA Topoisomerases, Type II