Squamous cell carcinoma of the oropharynx: Ki-67 and p53 can identify patients at high risk for local recurrence after surgery and postoperative radiotherapy

Purpose: To assess the prognostic value of biologic (p53, Ki-67) and clinic al factors in squamous cell carcinoma of the oropharynr after radical surge ry and postoperative radiotherapy (RT). Methods and Materials: Between 1985 and 1995, a total of 102 patients with 104 tumor sites were entered onto the study. Fifty-five primary tumors (53% ) involved the tonsils, 26 (25%) the soft palate, and 23 (22%) the base of the tongue. Median age was 53 Sears (range 36-80 gears). The clinical T- an d N-categories (UICC 1997) mere: T1 (30), T2 (47), T3 (22), T4 (5), N0 (33) , N1 (28), N2 (42), and N3 (1). Histologically-clear margins were achieved in all patients by initial surgery. Postoperative RT to the primary and reg ional lymphatics was given, to a total of 60 Gy in 6 weeks, and single dail y fractions of 2 Gy. The expression of the nuclear p53 and Ki-67-labeling i ndex (LI) was investigated by immunostaining using the monoclonal antibodie s DO-7 and RW 1. The nuclear p53-intensity (p53-I was graded into 4 categor ies (O/+/++/+++) by densitometry. Median follow-up was 33 months (range 14- 132 months). Results: Cancer-specific survival, disease-free survival, and locoregional tumor control rates were 74%, 69%, and 75%, respectively, at 5 years. Signi ficant prognostic factors for disease-free survival were: T-category (T1/2: 77% vs. T3/4: 53%, p = 0.02), tumor site (tonsils: 79% vs. soft palate: 70 % vs. base of tongue: 45%,p = 0.05), duration of RT (less than or equal to 46 days: 80% vs. > 46 days: 60%,p = 0.04), Ki-67 LI (less than or equal to 20% 84% vs. > 20%: 49%,p = 0.006) and p53-I (0/+: 58% vs. ++/+++: 79%, p = 0.008). A significant prognostic impact on locoregional control was noted f or the duration of RT (less than or equal to 46 days: 86% vs. > 46 days: 68 %,p = 0.01), tumor site (tonsils: 88% vs. soft palate: 67% vs. base of tong ue: 51%, p = 0.02), Ki-67 LI (less than or equal to 20% LI: 87% LI: 87% vs. > 20% LI: 56%,p = 0.018), and the p53-I (0/+: 58% vs. ++/+++: 88%, p = 0.0 006). On multivariate analysis, the p53 nuclear intensity (p = 0.002) and t he Ki-67 index (p = 0.01) remained the only significant factors for locoreg ional control. Conclusion: Ki-67 labeling index above 20% and a weak p53 nuclear intensity (0/+) are both able to identify patients with squamous cell carcinoma of t he oropharynx being at high risk for local recurrence after surgery and pos toperative RT. Consequently, in this subgroup an intensification of treatme nt may be contemplated in prospective trials. (C) 2000 Elsevier Science Inc .