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ras Gene Mutations as a Prognostic Marker in Adenocarcinoma of the Human Lung without Lymph Node Metastasis¹

Departments of Surgery II, Faculty of Medicine [K. S., Te. I., H. Y., Ta. I., K. S.], and Genetics, Medical Institute of Bioregulation [T. S.], Kyushu University, Fukuoka 812, Japan

Adenocarcinoma of the lung obtained at surgical resection was examined for mutation at codons 12, 13, and 61 of the oncogenes K-ras, H-ras, and N-ras, using polymerase chain reaction and oligonucleotide hybridization techniques. The mutation was detected in 18 of the 115 cases (15.7%), and 15 of 18 were at codon 12, 2 were at codon 13 of K-ras, and 1 was at codon 61 of N-ras. G to T transversions were most common. The ras gene mutations were more frequent in the male patients (P = 0.0048). No significant differences were found to be related to stage of the disease or tumor-nodes-metastases classification between positive and negative groups of the ras gene mutations. A history of tobacco use was not always a factor contributing to mutation. Of the completely resected group without lymph node metastasis, the 5-year survival rate in the ras-positive group was 53.3%, which was significantly poorer than the 83.6% survival rate in the ras-negative group (P < 0.05). Our findings suggest that ras gene mutations may be prognostic, especially in the early stage adenocarcinoma of the lung.

¹ This work was supported in part by Grant-in-Aid for General Scientific Research 03670659 from the Ministry of Education, Science and Culture, Japan.

² To whom requests for reprints should be addressed.

Received 12/10/91. Accepted 3/ 6/92.

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