Nuclear accumulation of p53 is a potential marker for the development of squamous cell lung cancer in smokers

Study objectives: To determine whether the nuclear accumulation of p53 in patients with early bronchial neoplasia. represents an altered susceptibility for the development of lung cancer. Patients and measurements: We evaluated the percentage of cells accumulating nuclear p53 immunohistochemically in squamous cell carcinoma (SCC) of the lung, the associated uninvolved bronchial mucosa, and epithelial hyperplasia in 60 archival lung specimens of smokers and in the normal bronchial epithelium and hyperplastic lesions of 60 smokers who had not developed lung cancer. Results: The percentage of cells accumulating p53 was significantly higher in SCC-associated uninvolved. bronchial epithelia of (mean [+/- SD], 4 +/- 0.9%) and in specimens from patients with epithelial hyperplasia (mean, 9 +/- 2%) compared to the percentage of cells from the bronchial epithelia of (mean, 0.5 +/- 0.2%) and in specimens from patients with epithelial hyperplasia (mean, 1.5 +/- 0.5%) who were smokers who had not developed lung cancer (p = 0.0002 and p = 0.0004, respectively). We also observed a statistically significant stepwise increase in the percentage of cells accumulating p53 from SCC-associated uninvolved bronchial epithelium to those from a patient with epithelial hyperplasia to those from a patient with SCC (mean, 35 +/- 4%), suggesting the involvement of p53 accumulation in the development of SCC (p less than or equal to 0.05 for all comparisons). The accumulation of p53 in SCC cells was not significantly associated with the size of the tumor, nodal involvement, the stage of the disease, the presence or absence of metastasis, the grade of differentiation, or survival of the disease, indicating its lack of association with the clinical progression of the disease. Conclusions: These results suggested that p53 accumulation is an early event in lung carcinogenesis and potentially could he useful in die identification of smokers who are at risk of developing SCC, but not in the estimation of survival of the disease.