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Prognostic Value of Nuclear DNA Content and Expression of the ras Oncogene Product in Lung Cancer¹

First Department of Medicine [H. M., M. H., H. I., H. D. A., H. H., E. Y., Y. K.], and the Laboratory of Molecular Genetics [N. K.], Cancer Institute, Hokkaido University School of Medicine, Sapporo 060, Japan

We evaluated the prognostic significance of nuclear DNA content by flow cytometry and ras oncogene expression in paraffin-embedded sections of tumors obtained surgically from 112 non-small cell lung cancer patients. Sixty-five (77%) of the 84 tumors had DNA aneuploid patterns that were statistically higher in adenocarcinoma than in squamous cell carcinoma. Of the 91 patients analyzed immunohistochemically using anti-ras M_r 21,000 protein (p21) monoclonal antibody rp-35, positive reactions (weak and strong) were observed in 56% of squamous cell carcinomas and 68% of adenocarcinomas. A better 5-yr survival rate was observed in the DNA diploid group (61%) than in the DNA aneuploid group (35%) (P < 0.01). Patients with p21-negative tumors survival significantly longer (5-yr survival rate of 64%) than did those with p21-weak tumors (38%, P < 0.05) or those with p21-strong tumors (12%, P < 0.01). Cox's multivariate analysis showed that DNA ploidy, ras p21 expression, and the stage of the disease were significant prognostic factors for survival. However, the DNA content was not a major independent prognostic factor in adenocarcinoma. The intensity of ras p21 expression was not correlated with nuclear DNA content. These results suggest that DNA content or enhanced ras p21 expression may be different biological markers indicating the malignant potential of lung tumors.

¹ This work was supported in part by a Grant-in-Aid (02404040) from the Ministry of Education, Science, and Culture, Japan.

² To whom requests for reprints should be addressed, at First Department of Medicine, School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo 060, Japan.

Received 4/24/91. Accepted 9/20/91.