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A Pilot Evaluation of Micrometastases for the Prediction of Outcome in Lung Cancer* FREE TO VIEW

Austin B. Thompson, MD, FCCP; Anne Kessinger, MD; J. Graham Sharp, PhD
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*From the Departments of Internal Medicine (Drs. Thompson and Kessinger) and Genetics, Cell Biology and Anatomy (Dr. Sharp), University of Nebraska Medical Center, Omaha, NE.

Correspondence to: Austin B. Thompson, MD, FCCP, Associate Professor of Medicine, Pulmonary and Critical Care Medicine Section, Department of Internal Medicine, 985300 Nebraska Medical Center, Omaha, NE 68198-5300; e-mail: athompso@unmc.edu

Chest. 2004;125(5_suppl):156S-157S. doi:10.1378/chest.125.5_suppl.156S-a
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The failure of surgical resection to cure all patients with early-stage (ie, stage I and II) non-small cell lung cancers (NSCLCs) suggests that some of these patients may have early micrometastases (MMs). In contrast, some earlier stage small cell lung cancers (SCLCs) have been associated with marrow MMs. In studies of lymph node-negative breast cancer, patients with marrow positive for MMs have significantly poorer outcomes.

To evaluate whether early MMs predicted outcomes in patients with lung cancer, 24 patients undergoing surgical resection of suspected stage I or II lung cancer consented to donate blood and bone marrow samples. For the 24 subjects, the final pathologic diagnoses were as follows: benign disease, 5 patients; leiomyosarcoma, 1 patient; SCLC, 7 patients; and NSCLC, 11 patients. Mononuclear cells were separated from blood and marrow samples using lymphocyte separation medium, and cytospins of 50 to 100,000 cells were prepared. These were stained immunocytochemically using the CAM 5.2 and MAK-6 cocktails of antibodies, which were validated against a spectrum of American Type Culture Collection (Manassas, VA) lung cancer cell lines.

None of the subjects with benign disease or leiomyosarcoma had evidence of MMs. All of the NSCLC subjects were negative for MMs. Five of the SCLC subjects were found to have marrow MMs, and all died within 6 to 14 months of diagnosis. Two SCLC subjects had marrow negative for MMs and are alive at 48 and 49 months (p = 0.05 for marrow MMs positive vs negative). Data for blood-borne MMs were available for five of the SCLC subjects. Blood-borne MMs were not predictive of survival. The results were in agreement in three subjects, the marrow was negative for MMs and blood was positive for MMs in one patient, and marrow was positive for MMs and blood was negative for MMs in one patient.

These preliminary results suggest that the absence of marrow MMs may predict survival in patients with SCLC.

Abbreviations: MM = micrometastasis; NSCLC = non-small cell lung cancer; SCLC = small cell lung cancer

This research was supported by grants from the Nebraska Department of Health.




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