The pathogenetic mechanism of gonadal dysgenesis and malignant germ cell tumours

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460427
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Tokyo Metropolitan Children's Medical Center (Department of Clinical Research) (2014-2015); Tokyo Metropolitan Institute of Medical Science (2013)
• Principal Investigator: Fukuzawa Ryuji 東京都立小児総合医療センター(臨床研究部), その他部局等, その他 (40245543)
• Co-Investigator(Renkei-kenkyūsha): Nishina Noriko 東京都立小児総合医療センター, 臨床研究部・その他の部局等, その他 (80649616)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 性分化異常 / 性腺芽腫 / 胚細胞腫瘍 / 混合性性腺異形成 / 真性半陰陽 / WT1 / SF1

Outline of Final Research Achievements

The purpose of this study was to establish pathological diagnostic methods for Disorders of Sexual Development (DSD) and to clarify the pathogenetic mechanism of tumorigenesis in DSD. We examined histologic features of gonads associated with NR5A1 mutations, StAR mutations, WT1 mutations, and mixed gonadal dysgenesis. We found that characteristic testicular histology is useful for the identification of mutations in the NR5A1 gene. We examined molecular and histological characteristics of 40 patients with DSD (5 Denys-Drash syndrome and 35 mixed gonadal dysgenesis) who predispose to malignant germ cell neoplasms. While gonadoblastomas were found in undifferentiated gonadal tissues, no germ cell tumors were detected. We established useful diagnostic methods for DSD patients to promptly and accurately determine their social gender. Our results indicate that the risk of developing germ cell tumor in DSD might be lower than it has been thought. Thus, excessive treatments should be avoided.

Free Research Field

人体病理学