P53 ONCOPROTEIN OVEREXPRESSION CORRELATES WITH MUTAGEN-INDUCED CHROMOSOME FRAGILITY IN HEAD AND NECK-CANCER PATIENTS WITH MULTIPLE MALIGNANCIES

In this study, we analysed immunocytochemically p53 expression in firs t primary and second primary cancers from 25 head and neck cancer pati ents (HNCPs) with multiple malignancies in comparison with oncoprotein expression in tumour tissues from 25 historical HNCP controls with si ngle cancer in a match-paired analysis. Moreover, we investigated bleo mycin-induced chromosome fragility in both groups of HNCPs and in 21 a dditional healthy controls. Thirty-nine out of 75 tumour specimens ana lysed (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 multipl e primary cancers, nine patients (36%) showed positive staining of bot h first and second primaries, whereas six (24%) had positive labelling of first primary cancer but not of the subsequent second primary, fou r (16%) patient showed p53 expression only in the second primary cance r and six (24%) patients showed no p53 immunoreactivity in both rumour s. Chromosomal analysis demonstrated a higher sensitivity to clastogen s of HNCPs with multiple tumours than of HNCPs with a single cancer (P < 0.01), and a significant correlation between chromosome fragility a nd p53 overexpression (P < 0.01) only in HNCPs with multiple malignanc ies more than in those with single head and neck cancer (P = 0.11). Mo reover, we found that patients with p53-positive staining of both firs t and second primaries showed a statistically significant higher mutag en sensitivity than those with a single p53 immunoreactive tumour or t hose in whom both cancers were p53 negative (P < 0.01). Our data sugge st that subjects with increased susceptibility to carcinogens after ex posure to tobacco or alcohol are at higher risk for multiple cancers i n which one of the most common genetic events is aberrant p53 expressi on.