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Determination of the Molecular Relationship Between Multiple Tumors Within One Patient Is of Clinical Importance

From the Department of Surgical Oncology, Dr Daniel den Hoed Clinic, and Departments of Pulmonology and Thoracic Surgery, University Hospital Dijkzigt; and Department of Pathology, Josephine Nefkens Institute, Erasmus University Medical Center Rotterdam, the Netherlands.

Address reprint requests to Winand N.M. Dinjens, PhD, Department of Pathology, Josephine Nefkens Institute, Erasmus University Medical Center Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, the Netherlands; email: dinjens{at}path.fgg.eur.nl

PURPOSE: To determine the molecular relationship between multiple tumors within one patient and to evaluate the impact of this knowledge on clinical management.

PATIENTS AND METHODS: In 25 consecutive patients with multiple tumors, proven by histology and immunohistochemistry to be identical, molecular aberrations were determined. Each patient had at least one lesion in the lung or head and neck region. Loss of heterozygosity (LOH) and p53 aberration analyses were carried out, and similar aberration profiles suggest clonality and metastasis whereas different profiles suggest independent primary tumors.

RESULTS: The molecular determinations indicated that 12 patients had a probable second primary tumor and 10 patients had a metastasis of the first lesion. In three patients, both an independent primary tumor and a metastasis were present. The molecular findings determined the course of additional treatment in all 10 patients with metastases, in all three patients with both a second primary tumor and a metastasis, and in seven of 12 patients with a second primary tumor.

CONCLUSION: By comparing DNA alterations of multiple tumors within one patient, the relationship between the tumors can be assessed. This study shows that in 20 of 25 patients, knowledge of the nature of both lesions was essential in clinical decision making. Furthermore, after thorough analysis of the five cases where clinical decision making was not influenced, there was in retrospect no clear indication for LOH or p53 analysis. Because these molecular analyses can be performed on routine specimens, they can be applied in almost all patients.

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