Determination of the molecular relationship between multiple tumors within one patient is of clinical importance.
OBJECTIVE
To determine the molecular relationship between multiple tumors within one patient and to evaluate the impact of this knowledge on clinical management.


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.


CONCLUSIONS
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.
van der Sijp
Joost R M
JR
Department of Surgical Oncology, Dr Daniel den Hoed Clinic, University Hospital Dijkzigt, the Netherlands.
van Meerbeeck
Jan P A M
JP
Maat
Alex P W M
AP
Zondervan
Pieter E
PE
Sleddens
Hein F B M
HF
van Geel
Albert N
AN
Eggermont
Alex M M
AM
Dinjens
Winand N M
WN
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000032:analysis*; D003657:Decision Making; D003937:Diagnosis, Differential; D005260:Female; D016158:Genes, p53; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D009378:Neoplasms, Multiple Primary / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D017931:DNA Primers; D004273:DNA, Neoplasm