Background. Glutathione (GSH) is important in in vitro models of radia
tion and drug resistance, but its clinical relevance is uncertain. GSH
levels were measured prospectively in 35 patients with breast cancer
to establish normal ranges and to determine whether differences exist
between tumor, lymph node metastases (when present), and normal breast
tissue. Methods. Fresh tissue was obtained immediately from discarded
surgical specimens, and total GSH levels were measured with the Tietz
e cyclic reduction assay. When possible, multiple sites were assayed i
n each tumor to assess intratumor variability. Results. GSH levels in
primary breast tumors were more than twice the levels found in normal
breast tissue, and levels in lymph node metastases were more than four
times the levels in normal breast tissue. The levels of GSH in normal
lymph nodes were similar to levels in normal breast tissue. GSH level
s in different areas of the same breast tumor ranged from below those
of normal breast tissue up to 11 times normal tissue levels. No correl
ation was found between tumor GSH levels and common clinical parameter
s such as tumor size, nodal status, stage, estrogen receptor levels, o
r progesterone receptor levels. Conclusions. GSH appears to be a marke
r of breast malignancy that is independent of hormonal receptor status
and stage and may be a marker of cells with increased potential for d
issemination. Because of tumor heterogeneity, multiple sites should be
sampled whenever possible. Long-term clinical follow-up will be neces
sary to ascertain the usefulness of tumor and lymph node GSH levels in
predicting prognosis.