CHICAGO--Researchers have identified a promising biochemical marker in the bone marrow of patients with metastatic non-small-cell lung cancer (NSCLC). [1] If the marker proves sufficiently sensitive and specific for metastatic disease, it could be extremely useful for identifying, staging, and treating patients with NSCLC.

"There are currently no good markers outside the tumor to determine whether [it] has recurred," said Thomas A. D'Amico, MD, an Assistant Professor in the Division of Cardiothoracic Surgery at Duke University Medical Center in Durham, North Carolina.

"The way we stage and evaluate tumors, based on routine histologic variables, including tumor size [and] obvious lymph node metastases, is not adequate. We need to find innovative ways to identify tumors elsewhere in the body," he added.

Dr. D'Amico and his colleagues conducted a study to identify a potential NSCLC marker that could be found in bone marrow. The researchers examined messenger RNA from the bone marrow of 34 patients with suspected or proven NSCLC. They presented their results at the recent annual meeting of the American College of Surgeons in Chicago.

Cytokeratin 19--which is found on the surface of tumors--was present in the bone marrow of five of the 21 patients (24%) with confirmed early stage lung cancer and in three of eight patients (38%) with advanced disease. The marker was not found in the bone marrow of any of the five patients with benign lung masses.

"We found that the marker can be picked up in bone marrow. Because the marker isn't found in normal patients, we know that patients with cytokeratin 19 have a high likelihood of disease recurrence [even] after a complete surgical resection for lung cancer," Dr. D'Amico said in an interview with PULMONARY REVIEWS.

The prognostic significance of this marker remains unclear, however. "The real test will be when we study patients to find out whether the presence of cytokeratin 19 truly predicts survival," he noted.

IMPLICATIONS FOR STAGING AND TREATMENT

Another important area of investigation, according to Dr. D'Amico, is to determine whether cytokeratin 19 can be identified somewhere else in the body. Dr. D'Amico and his colleagues hope to develop a blood test for this marker, which could be used to screen healthy patients for lung cancer. "A blood test could [also] be used to follow patients who have been treated for lung cancer to determine whether they responded to therapy or have recurrence of the disease and need to be treated again," suggested Dr. D'Amico.

"It could also be used at the time of surgery to determine whether a patient needs chemotherapy. To date, patients with stage I or II lung cancer are not given chemotherapy. However, a fraction of these patients (30% of [those with] stage I and 40% to 50% of [those with] stage II) are going to have a recurrence. It's possible that giving chemotherapy to this subset of patients might improve survival," said Dr. D'Amico.

Currently, the researchers are following a group of patients who have cytokeratin 19 in their bone marrow to determine three- to five-year survival rates. If they find a correlation between the presence of the marker and survival, Dr. D'Amico explained, the next step would be to perform a prospective study to determine whether aggressive chemotherapy would improve survival in patients with high levels of cytokeratin 19.

Although the findings are preliminary, Dr. D'Amico said he hopes this study will lead to more research and, ultimately, to better ways of identifying tumors and improving survival.

"We need to raise awareness that we can do better at staging patients than we're currently doing," he concluded.

--Deborah L. O'Connor

Reference
1. Aloia TA, Harpole DH Jr, D'Amico TA. Cytokeratin-19 is superior to mucin-1 as a marker of micrometastases in patients with non-small-cell lung cancer. Paper presented at: Annual Meeting of the American College of Surgeons. October 25, 2000; Chicago.

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