p53 expression: a potential biomarker for risk of multiple primary malignancies in the upper aerodigestive tract.

The concept of field cancerisation assumes that in head and neck cancer patients (HNCP) with multiple malignancies the second primary cancers may arise independently from the entire upper aerodigestive tract as a consequence of massive exposure to common carcinogens. Since mutations and/or overexpression of the p53 tumour suppressor gene represent a genetic alteration frequently occurring in HNCP, we analysed immunocytochemically p53 oncoprotein expression in first primary, second primary cancers and in macroscopically uninvolved normal epithelium from different sites of the upper aerodigestive tract from 12 HNCP with multiple malignancies, in comparison with p53 expression in biopsy specimens of the upper aerodigestive tract from 5 non-neoplastic heavy smokers, as controls. In patients with multiple malignancies 6 cases (50%) showed positive staining of both first and second primaries, whereas 3 (25%) had positive labelling of first primary cancer but not of the subsequent second primary, 2 (17%) patients showed p53 expression only in the second primary cancer, and finally only 1 patient (8%) showed no p53 immunoreactivity in both first and second primary tumours. Moreover, 10 out of 12 (83%) HNCP with multiple cancers showed p53-positive staining in the normal epithelium from different sites of the upper aerodigestive tract, also at a significant distance from the site of first and second primary malignancies. contrast, sporadic p53 immunostaining was observed only in three out of 35 (8.5%) specimens from non-neoplastic controls. In addition, in 4 HNCP with multiple tumours the histological examination of apparently normal epithelium from the upper aerodigestive tract revealed signs of moderate or severe dysplasia, and in 1 case an in situ carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)