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 predominantly intracellular protein thiol compounds involved in anticancer drug resistance. For certain tumors, MT is related to grade of tumor malignancy and prognosis. The authors evaluated the expression of MT in 114 astrocytic tumors in relation to the proliferative potential of tumors and the survival of patients. METHODS Paraffin embedded tissue sections were stained with monoclonal antimetallothionein 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 endothelial proliferation and smooth muscle of tumor vessel walls were frequently MT positive. The glioblastomas had a significantly higher percentage 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 (LI) was significantly higher in the high grade (3‐4) compared with the low grade (1‐2) astrocytomas. MT positive astrocytic tumors had statistically significantly higher mean Ki‐67 LI compared with MT negative tumors, 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 attained statistical significance only for glioblastoma. MT positive anaplastic astrocytoma and glioblastoma patients did not survive as long as the MT negative patients, although this difference attained statistical significance only for anaplastic astrocytoma. CONCLUSIONS The current 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. Cancer 1998;83:2361‐2369. © 1998 American Cancer Society. The expression of metallothionein (MT) in astrocytic tumors correlates with histologic grade and tumor Ki‐67 labeling index. In this study, MT positive anaplastic astrocytoma and glioblastoma patients did not survive as long as those who were negative. Because MT is related to cisplatin resistance, it may be beneficial to assess the MT level in tumors during cisplatin chemotherapy for patients with astrocytic tumors.