KI-67 AND P53 IN T2 LARYNGEAL-CANCER

Objective: To study the relationship between the proliferative capacit y, represented by the immunohistochemical labeling index (LI) of proli feration marker Ki-67, and the p53 status, as in theory an intact p53 cell cycle checkpoint system should result in a lower proliferative ca pacity. Study Design: From a group of 128 patients with a T2 laryngeal carcinoma, presented from 1989 to 1993 at the University Hospital Utr echt, 20 patients with recurrent disease and 16 patients without recur rent disease were randomly selected. All patients received primary irr adiation. Methods: Denaturing gradient gel electrophoresis and immunoh istochemistry determined the p53 status. MIB-1 staining was used to de termine the Ki-67 LI. Results: In 36% of specimens we found a p53 muta tion with overexpression (LI, 31%). In 8% a p53 mutation without p53 o verexpression was found (LI, 18%). Forty-two percent showed no mutatio n but, nevertheless, overexpression (LI, 35%). Neither mutation nor ov erexpression was found in 14% (LI, 38%). No correlation exists between p53 status and proliferative capacity of tumors (analysis of variance [ANOVA]; P =.104). The proliferation rate as established with Ki-67 L I positively correlates with response to radiotherapy (P =.006). Concl usions: 1. Overexpression of wild-type p53 protein does not result in cell cycle arrest measurable by a lower Ki-67 LI in comparison with ca ses overexpressing mutant type p53 protein. 2. A high Ki-67 LI correla tes with a favorable response to radiotherapy.