Shareholders as Stakeholders: A Future Paradigm for Institutional Activism in Japan

Over the last quarter century, the landscape of Japanese corporate governance has been overhauled by a combination of domestic reform, financial collapse, and foreign influence. Amidst these changes, institutional investors have claimed a growing role within Japanese listed companies, not only as monitors of management but as crucial agents for corporate governance reform. In this new role, institutional investors have adopted a diverse array of strategies and tactics for their dealings with management. This paper explores the future contours of Japanese shareholder activism against the backdrop of Japan’s twenty-first century corporate evolution. In particular, it analyzes how Japan’s modern corporate governance regime alters the behavior of institutional investors, and in turn the nature of their engagements with management of Japanese companies. Due to recent changes in Japanese law, Japan’s current governance standards limit the effectiveness of “aggressive” institutional activists. Rather than encourage contentious, highly public battles between adversarial activists and target companies, Japan’s current regime limits the opportunities for investment available to aggressive institutional investors by encouraging constructive engagement between investors and management. Although the quest for profits will continue to influence the behavior of investors and managers, Japan’s current regime invites institutions to act not only as profit-seeking shareholders, but also as stakeholders invested in the long-term financial stability of listed companies

Detection of MYCN Gene Amplification in Neuroblastoma by Fluorescence In Situ Hybridization: A Pediatric Oncology Group Study

To assess the utility of fluorescence in situ hybridization (FISH) for analysis of MYCN gene amplification in neuroblastoma, we compared this assay with Southern blot analysis using tumor specimens collected from 232 patients with presenting characteristics typical of this disease. The FISH technique identified MYCN amplification in 47 cases, compared with 39 by Southern blotting, thus increasing the total number of positive cases by 21%. The major cause of discordancy was a low fraction of tumor cells (≤30% replacement) in clinical specimens, which prevented an accurate estimate of MYCN copy number by Southern blotting. With FISH, by contrast, it was possible to analyze multiple interphase nuclei of tumor cells, regardless of the proportion of normal peripheral blood, bone marrow, or stromal cells in clinical samples. Thus, FISH could be performed accurately with very small numbers of tumor cells from touch preparations of needle biopsies. Moreover, this procedure allowed us to discern the heterogeneous pattern of MYCN amplification that is characteristic of neuroblastoma. We conclude that FISH improves the detection of MYCN gene amplification in childhood neuroblastomas in a clinical setting, thus facilitating therapeutic decisions based on the presence or absence of this prognostically important biologic marker

Lack of Homozygously Inactivated p73 in Single-Copy MYCN Primary Neuroblastomas and Neuroblastoma Cell Lines

We examined 18 neuroblastoma cell lines and 32 primary single-copy MYCN tumor specimens to determine whether mutations of p73, a novel p53-related gene located in chromosome band 1p36.33, contribute to the genesis or progression of childhood neuroblastoma. By fluorescence in situ hybridization, 16 of the 18 cell lines, but only 3 of the 32 primary tumors, had evidence of a deleted p73 allele. Sequence analysis of the p73 coding region in the mRNAs expressed by these cell lines and tumors did not reveal inactivating mutations, suggesting that p73 is not homozygously inactivated in neuroblastoma. However, several novel splice forms of p73 mRNAs were identified, including one without exon 11 that predominated in multiple MYCN-amplified cell lines. Its encoded p73 protein differed from other splice forms in that the C-terminus was derived from an alternative reading frame. Further study of the functional properties of the protein encoded by this splice form of p73 will be needed to determine whether it contributes to the pathogenesis of childhood neuroblastoma with MYCN gene amplification