5—Bromodeoxyuridine （BrdU）を用いたヒト中枢神経系腫瘍の成長解析

A CELL KINETIC STUDY OF HUMAN CENTRAL NERVOUS SYSTEM TUMORS WlTH 5-BROMODEOXYURIDINE (BrdU)

　抄録　5—bromodeoxyuridine （BrdU）の投与を受けた種々の中枢神経系腫瘍患者から得た腫瘍組織を用い，抗BrdU抗体によるimmunoperoxidase法を応用してDNA合成期細胞の全腫瘍細胞に対する標識率（LI：labeling index）を求めた。Medullobtastomaおよびglioblastoma multiformeでは平均で10％を越す高いLIが得られたのに対し，ependymomaやmoderately anaplastic astrocytomaなどの比較的分化型のgliomaではほとんどの例で1％以下の低いLIが得られ，highly anaplastic astrocytomaではそれらの中間の値であった。肺原発のmetastatic adenocarcinomaでは平均で10％を越す高いLIであった。又，pituitary adenoma,meningioma,acoustic neurinomaでは大半が1％以下の低いLIを示したが，少数例で1％を越す比較的高いLIが得られた。これらの結果は，LIが大体において従来知られている各腫瘍の臨床上の態度と相関していることを示していた。しかしながら，形態学的に同一と診断された腫瘍においてもLIの間に差がみられ，個々の腫瘍の間で分裂能などの生物学的特性に明らかな差のあることが示された。したがって本法は，従来の形態学的所見を補って，腫瘍個々の病理診断や悪性度の判定などにより定量的な情報を提供し得るものと期待される。

Sixty-six patients with various types of central nervous system (CNS) tumors were given 150-200 mg/m² of 5-bromodeoxyuridine (BrdU) intrave-nously at the start of surgery, in order to label DNA synthesizing cells in the tumor with BrdU. The excised tumor specimens were fixed in chilled 70% ethanol for at least 12 hours, embedded in paraffin, and cut into 6-8 it thick sections. The tissue sections were deparaffinized, denatured with HCI, and stained by indirect peroxidase method using anti-BrdU monoclonal antibody as the first antibody. The percentage of labeled cells among total cells (LI: labeling index) was calculated in each tumor specimen.

The average of LIs was over 10% in glioblas-toma multiforme, medulloblastoma, and metastatictumor. On the other hand, the LIs were very low, i.e.less than 1% in most cases of ependymomas, mixed gliomas, and moderately anaplastic astrocy-tomas. In highly anaplastic astrocytomas, the average of LIs resulted in 7.4%. The LIs of slow-growing tumors, such as pituitary adenomas, meningiomas, acoustic neurinomas, were less than 1%, except in Nelson's syndrome and a few cases of meningiomas. The LIs obtained thus seem to correlate with the clinical behavior of each type of tumor. However, there was still a magnitude of differences in LIs between the tumors which were histopathologically alike.

These results indicate that the LI obtained by the immunohistochemical method using anti-BrdU monoclonal antibody may supplement the current histopathological diagnosis in characterizing as well as estimating the biological malignancy of individual CNS tumors.

This work was supported in part by grants PDT-159 from ACS and CA 13525 from NCI.