Correlation of p53 and the proto-oncogene eIF4E in larynx cancers: Prognostic implications

p53 abnormalities constitute the most frequent genetic alterations identifi ed in larynx cancers. p53 overexpression in histologically "tumor-free" sur gical margins correlates with a high recurrence rate. However, only 50-60% of tumors overexpress p53, The tumor marker eIF4E is overexpressed in 100% of larynx cancers, and overexpression of eIF4E in histologically "tumor-fre e" margins predicts a significantly higher recurrence. We undertook this st udy to correlate the expression of p53 and eIF4E in the tumors and surgical margins of squamous cell cancers of the larynx and to determine their prog nostic value, A retrospective analysis was performed on 54 patients who und erwent surgery for squamous cell cancers of the larynx. Patient and tumor c haracteristics were reviewed, and the time to recurrence was noted. Paraffi n-embedded sections from the tumors and surgical margins were immunostained with antibodies to eIF4E and p53, and a qualitative analysis was performed . All 54 patients (100%) overexpressed eIF4E in the primary tumor, whereas 25 of 53 patients (47%) were p53 positive. Thirty-two of the 54 patients (5 9%) had eIF4E-positive margins, All 6 of 53 patients (11%) with p53-positiv e margins also overexpressed eIF4E in the margins, There was a significant correlation between p53 and eIF4E being positive in the margins (Spearman's correlation coefficient, P = 0.03), Twenty-one of the 25 patients (84%) th at recurred, including the 6 patients with p53-positive margins, had eIF4E- positive margins, Hence, although the univariate analysis showed that nodal status and both eIF4E and p53 expression in the margins were significant p redictors of recurrence (P < 0.05), in the multivariate analyses only nodal status (P < 0.001) and eIF4E in the margins (P < 0,001) were significant p redictors of recurrence, Kaplan-Meier analysis demonstrated that the diseas e-free intervals for eIF4E-positive margins were significantly shorter than eIF4E-negative margins (P = 0.0007), There was no additional effect to the combination of positive p53 and eIF4E margins (P = 0.21), The overexpressi on of eIF4E in the margins appears to be a more sensitive indicator of recu rrence and may be an earlier event In the process of tumorigenesis than p53 ,