HUMAN NONSMALL CELL LUNG-CANCER - P53 PROTEIN ACCUMULATION IS AN EARLY EVENT AND PERSISTS DURING METASTATIC PROGRESSION

Mutations in the p53 tumour suppressor gene, with consequent accumulat ion of the p53 protein, are frequently observed in non-small cell lung cancer (NSCLC). Little is known, however, about the timing of their a ppearance or their maintenance through cancer progression and metastat ic spread. We have examined the normal epithelium and a panel of bronc hial lesions, including dysplastic, neoplastic, and metastatic lesions , for p53 immunoreactivity and for expression of proliferating cell nu clear antigen (PCNA). No p53 immunoreactivity was found in normal and hyperplastic epithelium, nor in squamous metaplastic lesions. Twenty o ut of 30 invasive tumours and 13 out of 17 in situ carcinomas adjacent to an invasive tumour showed p53 immunoreactivity. There was a strict correlation between the level of p53 expression in the non-invasive a nd the invasive components of the tumours. Five out of eight pairs of primary tumours and matching metastases expressed p53, at identical le vels in both compartments. These data indicate that p53 overexpression can occur in the earliest recognized phase of NSCLC and that the alte ration is maintained during progression from in situ to invasive carci noma and metastatic spread. PCNA expression increased from early to ad vanced phases of NSCLC. High PCNA immunoreactivity was observed in tum ours expressing high p53 levels. A significant association was observe d for PCNA expression between preinvasive and invasive lesions.