T. Hiura et al., IMMUNOHISTOCHEMICAL ANALYSIS OF METALLOTHIONEIN IN ASTROCYTIC TUMORS IN RELATION TO TUMOR GRADE, PROLIFERATIVE POTENTIAL, AND SURVIVAL, Cancer, 83(11), 1998, pp. 2361-2369
BACKGROUND. Metallothionein (MT) is the name for a family of predomina
ntly intracellular protein thiol compounds involved in anticancer drug
resistance. For certain tumors, MT is related to grade of tumor malig
nancy and prognosis. The authors evaluated the expression of MT in 114
astrocytic tumors in relation to the proliferative potential of tumor
s and the survival of patients. METHODS. Paraffin embedded tissue sect
ions were stained with monoclonal anti-metallothionein and MIB-1 Ki-67
antibodies by avidin-biotin complex immunohistochemistry. RESULTS. MT
expression was observed in 2 of 6 pilocytic astrocytomas, in 10 of 24
Grade 2 astrocytomas, in 16 of 25 anaplastic astrocytomas, and in 47
of 59 glioblastomas. In addition to the tumor cells, microvascular end
othelial proliferation and smooth muscle of tumor vessel walls were fr
equently MT positive. The glioblastomas had a significantly higher per
centage of MT positive cells compared with low grade (P < 0.0001) and
anaplastic (P < 0.04) astrocytomas. MT expression in astrocytomas had
no correlation with tumor recurrence. The mean Ki-67 labeling index (L
I) was significantly higher in the high grade (3-4) compared with the
low grade (1-2) astrocytomas. MT positive astrocytic tumors had statis
tically significantly higher mean Ki-67 LI compared with MT negative t
umors, irrespective of histologic grade. Although the levels of MT and
Ki-67 LI varied in individual tumors, the mean Ki-67 LI increased in
parallel to the increasing MT staining grade, and this difference atta
ined statistical significance only for glioblastoma. MT positive anapl
astic astrocytoma and glioblastoma patients did not survive as long as
the MT negative patients, although this difference attained statistic
al significance only for anaplastic astrocytoma. CONCLUSIONS. The curr
ent study suggests that MT might play a significant role in the growth
of astrocytic tumors, with an acquired enhanced ability to produce MT
as the malignant potential of a tumor increases. (C) 1998 American Ca
ncer Society.