P53 and Ki-67 as outcome predictors for advanced squamous cell cancers of the head and neck treated with chemoradiotherapy

Abstract

Hypothesis: P53 and Ki-67 status will predict response to treatment, organ preservation, and survival in patients with advanced squamous cell cancers of the head and neck treated with chemoradiotherapy (CRT).

Study design: Retrospective analysis of p53 and Ki-67 status from the CRT arm of a randomized, controlled trial (n = 50) and from patients receiving the same treatment but not enrolled in the trial (n = 55).

Methods: P53 and Ki-67 status were established from archived tissue samples using immunohistochemical (IHC) staining. Tumors were positive for p53 (p53+) when more than 2% of cells stained for p53 and were positive for Ki-67 (Ki-67+) when any cell stained for Ki-67. End points were tumor response, tumor recurrence, survival status, and organ preservation at last follow-up, and time to events. Predictive models were calculated for each outcome.

Results: Neither marker predicted tumor response to treatment. P53+ status was associated with tumor recurrence (P =.003) and locoregional recurrence (P =.003). Adjusting for time to event, p53+ status was significantly related to a lower recurrence-free survival (P =.004), lower disease-specific survival (P =.04), lower overall survival with primary site preservation (P =.03), and lower disease-specific survival with primary site preservation (P =.003). Multivariate analysis revealed that p53+ status was significantly related to a lower recurrence-free survival (P =.01, risk ratio [RR] = 3.65) and lower disease-specific survival with organ preservation (P =.02, RR = 3.41). Ki-67+ status was not related to any variables. However, multivariate analysis revealed that Ki-67+ was significantly related to a lower overall survival (P =.05, RR = 2.03). The combination of both markers negative (p53-/Ki-67-) was associated with a lower incidence of tumor recurrence (P =.02), lower locoregional recurrence (P =.01), and fewer second primary lesions (P =.04). Adjusting for time to event, p53-/Ki-67- status was significantly related to a higher recurrence-free survival (P =.02), higher disease-specific survival with primary site preservation (P =.02), and higher overall survival with primary site preservation (P =.02). Multivariate analysis revealed that p53-/Ki-67- status was significantly related to a higher overall survival with site preservation (P =.01, RR = 2.78).

Conclusions: P53 and Ki-67 status appear to be related to the various survival end points considered in this study. However, this relation does not seem to be sufficient to warrant treatment modifications. Closer follow-up may be justified in both p53+ and Ki67+ patients to detect recurrence or a second primary at an earlier stage, possibly improving survival.