IMMUNOHISTOCHEMICAL ANALYSIS OF METALLOTHIONEIN IN ASTROCYTIC TUMORS IN RELATION TO TUMOR GRADE, PROLIFERATIVE POTENTIAL, AND SURVIVAL

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.