High Expression and Diagnostic Utility of Internexin alpha in Clear Cell Sarcoma of the Kidney: Comparative Proteomics Analysis and Immunohistochemical Study
Yukichi Tanaka, Akira Katayama, Takeshi Inoue, Hideo Iwafuchi, Hiroshi Kishimoto, Masayuki Nakayama, Noriyuki Nagahara, Hideo Orimo, Minoru Hamazaki, Mio Tanaka, Mariko Yoshida, Rieko Ijiri, Norihiko Kitagawa, Masato Shinkai, Hisato Kigasawa. Kanagawa Children's Medical Center, Yokohama, Kanagawa, Japan; Nippon Medical School, Bunkyo-ku, Tokyo, Japan; Osaka City General Hospital, Miyakojima-ku, Osaka, Japan; Shizuoka Children's Hospital, Shizuoka, Japan; Saitama Children's Medical Center, Saitama, Japan; Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Osaka, Japan
Background: Clear cell sarcoma of the kidney (CCSK) is the second most frequent pediatric renal tumor and is considered to be a highly malignant mesenchymal tumor. To date few specific biomarkers for CCSK have been identified. It is sometimes difficult to differentiate CCSK from other renal tumors on conventional histopathology and immunohistochemistry.
Design: To find more specific positive biomarkers for CCSK we performed comparative proteomics analysis, western blotting, and immunohistochemical study. By comparative proteomics analysis between fresh frozen samples of CCSK and congenital mesoblastic nephroma cellular type (CMN-C) which is a mostly non-aggressive mesenchymal tumor that may be morphologically misdiagnosed as CCSK, we found some candidate proteins that are contained predominantly in CCSKs. Among these proteins, we focused on internexin-alpha (INA), a class IV intermediate filament and an example of neural biomarkers. The specificity of INA-expression in CCSK was examined by western blotting and immunohistochemical study on various types of pediatric renal tumors, including 21 CCSKs, 27 nephroblastomas (25 with no anaplasia, 2 with anaplasia), 15 CMNs (10 CMN-Cs and 5 classical type), 8 rhabdoid tumors of the kidney (RTKs), 3 Ewing sarcoma family tumors (ESFTs), 2 synovial sarcomas (SSs), and 1 anaplastic sarcoma of the kidney (ASK).
Results: On western blotting, INA was detected not in CMN-Cs but in CCSKs. On immunohistochemical study, 21 CCSKs showed diffuse positivity for INA. Twenty-five nephroblastomas without anaplasia, 15 CMNs, 3 ESFTs, 2 SSs, and 1 ASK showed negative results. Two nephroblastomas with anaplasia and 6 of 8 RTKs showed scattered positivity for INA. In renal tissues adjacent to the tumors, positivity for INA was observed only in a few peripheral nerves.
Conclusions: INA is a considerably specific positive marker for CCSK and is promising in the differential diagnosis of pediatric renal tumors. Significance of high expression of this neural biomarker in this enigmatic tumor and its relevance to the extent of malignancy remains to be clarified.
Category: Genitourinary (including renal tumors)
Monday, March 4, 2013 1:00 PM
Poster Session II # 161, Monday Afternoon