Ikuma Kato1, Mitsuko Furuya1, Masaya Baba2, Yoichi Kameda3, Masanori Yasuda4, Koshiro Nishimoto5, Masafumi Oyama5, Toshinari Yamasaki6, Osamu Ogawa6, Hitoshi Niino7, Noboru Nakaigawa8, Yuta Yano9, Kazumasa Sakamoto10, Yoji Urata11, Kazuya Mikami12, Shigetaka Yamasaki13, Reiko Tanaka14, Toshio Takagi15, Tsunenori Kondo15, Yoji Nagashima16. 1. Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. 2. International Research Centre for Medical Sciences, Kumamoto University, Kumamoto, Japan. 3. Department of Pathology, Ashigarakami Hospital, Kanagawa, Japan. 4. Department of Pathology, Saitama Medical University International Medical Centre, Saitama, Japan. 5. Department of Urological Oncology, Saitama Medical University International Medical Centre, Saitama, Japan. 6. Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan. 7. Department of Pathology, National Hospital Organization Yokohama Medical Centre, Yokohama, Japan. 8. Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. 9. Department of Pathology, Tokyo Metropolitan Cancer and Infectious Diseases Centre Komagome Hospital, Tokyo, Japan. 10. Department of Urology, Tokyo Metropolitan Cancer and Infectious Diseases Centre Komagome Hospital, Tokyo, Japan. 11. Department of Pathology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan. 12. Department of Urology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan. 13. Department of Pathology, Tokyo Rinkai Hospital, Tokyo, Japan. 14. Medical Mycology Research Centre, Chiba University, Chiba, Japan. 15. Department of Urology, Tokyo Women's Medical University, Tokyo, Japan. 16. Department of Surgical Pathology, Tokyo Women's Medical University, Tokyo, Japan.
Abstract
AIMS: Xp11 rearrangement in renal cell carcinoma (RCC) typically involves gene fusion to the gene encoding transcription factor E3 (TFE3), a member of the microphthalmia-associated transcription factor family on chromosome Xp11.2. Dual-colour break-apart fluorescence in-situ hybridisation (FISH) is recommended to confirm histological diagnoses. Recently, RNA-binding motif protein 10 (RBM10), encoded by a gene on chromosome Xp11.3, was identified as a chimeric partner of TFE3; thus, RBM10-TFE3 fusion results from paracentric inversion. RBM10-TFE3 RCC may yield a false-negative result in FISH analysis of TFE3 expression. The aim of the present study was to investigate the clinicopathological features of RBM10-TFE3 RCC. METHODS AND RESULTS: Ten patients with RBM10-TFE3 RCC aged 31-71 years were investigated. Histological analysis, immunostaining, dual-colour break-apart FISH for TFE3, reverse transcription polymerase chain reaction and sequencing analysis were performed. No patient had a history of exposure to chemotherapy. Two of these patients died of RCC, and three were alive but developed metastases. Microscopically, the tumours were composed of a mixed architecture of tubulocystic and papillary patterns with scattered psammoma bodies. The tumours showed strong nuclear immunoreactivity for TFE3. FISH showed consistent closely spaced split signals in the RCCs of four patients, and polysomic signals with occasional closely spaced split signals in the RCCs of six patients. Of the latter six patients, five had renal failure, and four developed tumours in kidneys subjected to haemodialysis. CONCLUSIONS: The present study suggests that the carcinogenesis of RBM10-TFE3 RCC in some, but not all, patients may be associated with chronic kidney disease. The aggressive nature of RBM10-TFE3 RCC should be considered, as five patients experienced metastases.
AIMS: Xp11 rearrangement in renal cell carcinoma (RCC) typically involves gene fusion to the gene encoding transcription factor E3 (TFE3), a member of the microphthalmia-associated transcription factor family on chromosome Xp11.2. Dual-colour break-apart fluorescence in-situ hybridisation (FISH) is recommended to confirm histological diagnoses. Recently, RNA-binding motif protein 10 (RBM10), encoded by a gene on chromosome Xp11.3, was identified as a chimeric partner of TFE3; thus, RBM10-TFE3 fusion results from paracentric inversion. RBM10-TFE3RCC may yield a false-negative result in FISH analysis of TFE3 expression. The aim of the present study was to investigate the clinicopathological features of RBM10-TFE3RCC. METHODS AND RESULTS: Ten patients with RBM10-TFE3RCC aged 31-71 years were investigated. Histological analysis, immunostaining, dual-colour break-apart FISH for TFE3, reverse transcription polymerase chain reaction and sequencing analysis were performed. No patient had a history of exposure to chemotherapy. Two of these patients died of RCC, and three were alive but developed metastases. Microscopically, the tumours were composed of a mixed architecture of tubulocystic and papillary patterns with scattered psammoma bodies. The tumours showed strong nuclear immunoreactivity for TFE3. FISH showed consistent closely spaced split signals in the RCCs of four patients, and polysomic signals with occasional closely spaced split signals in the RCCs of six patients. Of the latter six patients, five had renal failure, and four developed tumours in kidneys subjected to haemodialysis. CONCLUSIONS: The present study suggests that the carcinogenesis of RBM10-TFE3RCC in some, but not all, patients may be associated with chronic kidney disease. The aggressive nature of RBM10-TFE3RCC should be considered, as five patients experienced metastases.