Variable genetic alterations and survival in head and neck cancer.

Abstract

To evaluate multiple genetic loci in patients with head and neck cancer to determine if, as in colorectal carcinoma, there is an orderly occurrence of genetic alterations, and if an accumulation of alterations affects patient survival. Cohort study of patients with head and neck cancer in which fresh tissue was retrieved. Academic medical center. Forty-three patients treated surgically for squamous cell carcinoma of the head and neck from 1991 to 1994. The DNA from tumor and healthy tissue was evaluated for loss of heterozygosity at p53, retinoblastoma, and chromosome 16q and for amplification of cyclin D1. The respective RNA was probed for levels of p53, p 16, p21, and p27 messenger RNA. These findings were compared with tumor stage and patient survival. DNA analysis showed that loss of heterozygosity occurred at p53 in 21% of tumors, at retinoblastoma in 35%, and at 16q in 21%, and that cyclin D1 was amplified in 42%. Messenger RNA levels of the assessed proteins were variably increased and decreased compared with healthy tissues obtained from the same patients with no discernable pattern. There was no correlation between any one of these genetic alterations and overall survival. When patients were analyzed for loss of heterozygosity at p53, retinoblastoma, 16q, or altered cyclin D1 in combination, 19 patients had no detectable alterations, 13 had 1, 6 had 2, and 5 had 3. Single genetic alterations did not affect survival; however, there was a trend toward decreased survival with multiple alterations. The 2-year Kaplan-Meier survival in patients with less than 1 genetic loss was 78% vs 58% in patients with 2 or more losses. The lack of a pattern of genetic alterations in head and neck cancer demonstrates that its progression can be mediated by a multitude of pathways, complicating its genetic evaluation. Single genetic alterations do not appear to affect survival; however, when multiple alterations are detected-regardless of combination-survival is affected. This observation lends credence to the theory that multiple genetic alterations contribute to cancer progression; however, the lack of a pattern of this genetic change is a significant obstacle to applying genetic findings to routine cancer therapy.