title: Squamous cell carcinoma of the oropharynx: Ki-67 and p53 can identify patients at high risk for local recurrence after surgery and postoperative radiotherapy.
abstract: OBJECTIVE
  To assess the prognostic value of biologic (p53, Ki-67) and clinical factors in squamous cell carcinoma of the oropharynx after radical surgery and postoperative radiotherapy (RT).
  
  
  METHODS
  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 years (range 36-80 years). The clinical T- and N-categories (UICC 1997) were: 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 regional lymphatics was given, to a total of 60 Gy in 6 weeks, and single daily fractions of 2 Gy. The expression of the nuclear p53- and Ki-67-labeling index (LI) was investigated by immunostaining using the monoclonal antibodies DO-7 and MIB 1. The nuclear p53-intensity (p53-I) was graded into 4 categories (0/+/++/) by densitometry. Median follow-up was 43 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. Significant 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 (< or = 46 days: 80% vs. > 46 days: 60%, p = 0.04), Ki-67 LI (< or = 20%: 84% vs. > 20%: 49%, p = 0.006) and p53-I (0/+: 56% vs. ++/ : 79%, p = 0.008). A significant prognostic impact on locoregional control was noted for the duration of RT (< or = 46 days: 86% vs. > 46 days: 68%, p = 0.01), tumor site (tonsils: 88% vs. soft palate: 67% vs. base of tongue: 51%, p = 0.02), Ki-67 LI (< or = 20% LI: 87% vs. > 20% LI: 56%, p = 0.018), and the p53-I (0/+: 58% vs. ++/ : 88%, p = 0.0006). On multivariate analysis, the p53 nuclear intensity (p = 0.002) and the Ki-67 index (p = 0.01) remained the only significant factors for locoregional control.
  
  
  CONCLUSIONS
  Ki-67 labeling index above 20% and a weak p53 nuclear intensity (0/+) are both able to identify patients with squamous cell carcinoma of the oropharynx being at high risk for local recurrence after surgery and postoperative RT. Consequently, in this subgroup an intensification of treatment may be contemplated in prospective trials.
authors.affiliation: Department of Radiation Oncology, University Hospital, Erlangen, Germany. gerd.grabenbauer@strahlen.imed.uni-erlangen.de
authors.forename: G G
authors.initials: GG
authors.lastname: Grabenbauer
authors.forename: C
authors.initials: C
authors.lastname: Mühlfriedel
authors.forename: F
authors.initials: F
authors.lastname: Rödel
authors.forename: G
authors.initials: G
authors.lastname: Niedobitek
authors.forename: J
authors.initials: J
authors.lastname: Hornung
authors.forename: C
authors.initials: C
authors.lastname: Rödel
authors.forename: P
authors.initials: P
authors.lastname: Martus
authors.forename: H
authors.initials: H
authors.lastname: Iro
authors.forename: T
authors.initials: T
authors.lastname: Kirchner
authors.forename: H
authors.initials: H
authors.lastname: Steininger
authors.forename: R
authors.initials: R
authors.lastname: Sauer
authors.forename: M
authors.initials: M
authors.lastname: Weidenbecher
authors.forename: L
authors.initials: L
authors.lastname: Distel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000175:diagnosis* / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis*; D010157:Palatal Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000628:therapy; D010160:Palate, Soft; D011879:Radiotherapy Dosage; D014062:Tongue Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000628:therapy; D014067:Tonsillar Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000628:therapy; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53