Microsatellite DNA alterations are an integral part of neoplastic prog
ression and are valuable as clonal markers for the detection of human
cancers(1-3). Moreover, recent evidence suggests that senescent tumor
cells may release DNA into the circulation, which is subsequently carr
ied by and therefore enriched in the serum and plasma(4,5). We tested
21 patients with primary head and neck squamous cell carcinoma (HNSCC)
by polymerase chain reaction (PCR)-based microsatellite analysis of D
NA from lymphocytes and paired serum samples. Patients were scored for
alterations as defined by the presence of new alleles (shifts) or los
s of heterozygosity (LOH) in serum at each of 12 markers and then comp
ared with primary tumor DNA. Six out of 21 patients (29%) were found t
o have one or more microsatellite alterations in serum precisely match
ing those in the primary tumors. All six patients had advanced disease
(stage III or IV); five of these patients had nodal metastases, three
later developed distant metastases, and four died of disease. Microsa
tellite analysis of serum represents a novel method for the detection
of circulating tumor cell DNA. If these results are confirmed in large
r studies, microsatellite markers may be useful in assessing tumor bur
den in cancer patients.