Active lung gene signals cancer spread.

Even when caught and removed early, lung cancer can be deadly. Roughly onefourth of patients treated for first-stage lung cancer--the kind showing no visible signs of having spread to lymph nodes or other tissues outside the lung--eventually die from a recurrence of the disease.

Scientists in Japan have now discovered a gene that may help physicians determine which patients are more likely to suffer such relapses. The gene, called LUNX, is active only in lung tissue and in tumor tissue that originated there and spread.

The finding could offer physicians a better way to detect cancer that has spread to nearby lymph nodes, the immune tissues that are usually the first stop for cancer outside the organ of its origin, says study coauthor Yoshiyuki Fujiwara, a surgical oncologist at Osaka University Graduate School of Medicine. The study appears in the February INTERNATIONAL JOURNAL OF CANCER.

After identifying the LUNX gene on chromosome 20, Fujiwara and his colleagues found that LUNX was active in all normal lung-tissue samples from 31 lung cancer patients. The researchers noted that the gene was revved up even more in nearly all the cancerous tissues from these patients. LUNX wasn't active in tissue samples from stomach, gallbladder, or bile duct cancers.

The researchers also tested for LUNX activation in lymph nodes from another 20 lung cancer patients. According to standard microscope observations of cells, the cancer had spread to nodes near the lungs in five of the patients. But Fujiwara's research team detected LUNX activation in lymph nodes of four of these people plus 11 others.

The scientists also examined 84 lymph nodes that had tested negative for cancer by standard methods even though the nodes came from lung cancer patients. Of these nodes, 21 tested positive for LUNX activity, suggesting that the cancer had spread beyond the lungs. LUNX activity was absent in 16 lymph nodes taken from people who had no cancer. Therefore, the test could help physicians identify the spread of cancer earlier than is possible by conventional tests, Fujiwara says.

"Potentially, this is very interesting," says David P. Carbone of Vanderbilt University Cancer Center in Nashville. But since physicians don't have a surefire treatment for lung cancer, particularly after it's spread, the value of the new gene test remains unclear, he says. Carbone notes that patients whose cancer has spread sometimes benefit from chemotherapy prior to tumor removal.

The scientists don't know what role the protein encoded by the LUNX gene plays. It may serve simply as a "housekeeping" protein in the lungs, says Curtis C. Harris of the National Cancer Institute in Bethesda, Md. As a target for new cancer drugs, he says, "you would like to have, if possible, a gene whose product is either essential to the maintenance of the cancer" or aids its spread.

The patients in this study had nonsmall-cell lung cancer, which accounts for four-fifths of lung cancers.