Objective: To understand the relationship between the expression of ras and p53 and histological types, degree of differentiation, TNM classification, stage, and patients?prognoses of non-small-cell lung cancer, we examined Ha-ras and p53 production in 143 non-small-cell lung carcinomas. Methods: One hundred and forty-three paraffin-embedded surgically resected specimens of primary non-small-cell lung carcinomas (57 squamous cell carcinomas, 63 acinar adenocarcinomas, 15 bronchio-loalveolar carcinomas, and 8 large-cell carcinomas) were stained by streptavidin-peroxidase immunohistochemical method using anti-Ha-ras monoclonal and anti-p53 monoclonal (DO-1) antibodies. Results: Ha-ras was found in 68% (87 of 143) of lung carcinomas. The positive rate of Ha-ras staining in well differentiated carcinoma was 89%, significantly higher than that in moderately differentiated carcinoma (66%, P<0.05) and that in poorly differentiated carcinoma (48%, P<0.01). The 5-year survival rates of patients whose tumors had no (39%, P<0.01) or moderate (33%, P<0.05) Ha-ras production were significantly higher than that of patients whose tumors had strong staining (14%) for Ha-ras. Sixty percent lung carcinomas (86 of 143) had p53 accumulation. Patients whose tumors did not express p53 survived, on average, significantly longer after tumor resection than did patients whose tumors expressed p53. With increasing p53 accumulation, the average length of survival after tumor resection significantly decreased. Conclusion: Ha-ras overproduction and p53 accumulation correlate with unfavorable prognoses of patients with non-small-cell lung carcinomas. Ha-ras production in non-small- cell lung carcinoma was related to the degree of differentiation.
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