Nitric oxide synthases (NOS) exist in human tumor cell lines and solid
tumor tissues, and it has been suggested that NO may play important r
oles in growth, progression or metastasis of tumors. We investigated t
he activity and distribution of NOS in a series of human lung cancer a
nd normal lung tissues. Seventy-two primary lung cancer samples (44 ca
ses of adenocarcinoma, 18 of squamous cell carcinoma, 4 of large cell
carcinoma, 2 of small cell carcinoma, 2 of adenosquamous carcinoma, an
d 2 of carcinoids) and corresponding normal lung samples were obtained
from surgically treated patients. In normal lung tissues, little NOS
activity was observed with no correlation between the patients' age an
d NOS activity. The total NOS activities in lung adenocarcinoma sample
s were significantly higher than those in other types of lung cancers
or normal lung samples (P<0.05). Analysis by tumor grade of the adenoc
arcinoma samples revealed no significant difference of NOS activity be
tween grades. TNM classification showed that, although T stage did not
correlate with NOS activity, cancer tissues from patients with N2 dis
ease tended to have lower activity than those from patients with N0 or
N1 disease. Immunohistochemical studies revealed that the intensity o
f NOS immunoreactivity correlated with NOS activity. These results sug
gest that NO may play an important role in the metabolism and behavior
of lung cancers, especially adenocarcinoma.