We examined the possibility of using microsatellite alterations as markers
to detect clonal tumor-derived cell populations in histopathologically nega
tive surgical margins and cervical lymph nodes from head and neck cancer (H
NC) patients. We used polymerase chain reaction (PCR)-based microsatellite
analysis DNA to analyze primary tumors, paired surgical margins, and cervic
al lymph nodes from 41 HNC patients. Samples were scored for alterations as
defined by the presence of new alleles (shifts) or loss of heterozygosity
(LOH) at each of 10 markers. We identified 25 (61%) patients with primary H
NC who appeared to have had a complete resection on the basis of the histop
athological assessment and who were informative regarding microsatellite al
terations in tumor tissue. In 11 of these 25 (44%) cases, PCR analysis of s
urgical margins showed the same microsatellite alterations as in the primar
y tumors. In 7 of these 11 patients, the carcinoma recurred locally, as com
pared with 1 out of 14 patients with negative margins (log rank test, P = 0
.0049). Conversely, we were unable to detect clonal neoplastic cells in his
topathologically negative lymph nodes examined by molecular analysis. Cox r
egression analysis showed that molecular positive margins were an independe
nt prognostic factor (P = 0.04) for recurrence. This study demonstrates tha
t microsatellite analysis may be a valuable tool for evaluating the risk of
local recurrence. (C) 2000 Wiley-Liss, Inc.