In this study, we analysed immunocytochemically p53 expression in first primary and
second primary cancers from 25
head and neck cancer patients (HNCPs) with multiple
malignancies in comparison with
oncoprotein expression in tumour tissues from 25 historical HNCP controls with single
cancer in a match-paired analysis. Moreover, we investigated
bleomycin-induced
chromosome fragility in both groups of HNCPs and in 21 additional healthy controls. Thirty-nine out of 75 tumour specimens analysed (52%) showed positive p53 immunostaining. Eleven out of 25 (44%) from single
cancer patients and 28 out of 50 (56%) tumours from HNCPs with multiple
malignancies were p53 positive. In the group of multiple primary
cancers, nine patients (36%) showed positive staining of both first and second primaries, whereas six (24%) had positive labelling of first primary
cancer but not of the subsequent second primary, four (16%) patient showed p53 expression only in the
second primary cancer and six (24%) patients showed no p53 immunoreactivity in both tumours. Chromosomal analysis demonstrated a higher sensitivity to
clastogens of HNCPs with multiple tumours than of HNCPs with a single
cancer (P < 0.01), and a significant correlation between
chromosome fragility and p53 overexpression (P < 0.01) only in HNCPs with multiple
malignancies more than in those with single
head and neck cancer (P = 0.11). Moreover, we found that patients with p53-positive staining of both first and second primaries showed a statistically significant higher
mutagen sensitivity than those with a single p53 immunoreactive tumour or those in whom both
cancers were p53 negative (P < 0.01). Our data suggest that subjects with increased susceptibility to carcingogens after exposure to tobacco or alcohol are at higher risk for multiple
cancers in which one of the most common genetic events is aberrant p53 expression.