Li-Fraumeni syndrome with simultaneous osteosarcoma and liver cancer: Increased expression of a CD44 variant isoform after chemotherapy

BMC Cancer

Case Report

Hideo Morioka¹  Seiichi Hosaka¹  Michiie Sakamoto²  Yohei Masugi²  Tatsuo Kuroda³  Tomoo Osumi⁴  Hiroyuki Shimada⁴  Makio Mukai⁵  Go J Yoshida⁶  Yasushi Fuchimoto⁷ 

[1] Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Japan;Department of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, 1608582, Tokyo, Japan;Department of Pediatric Surgey, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, 1608582, Tokyo, Japan;Department of Pediatrics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, 1608582, Tokyo, Japan;Division of Diagnostic Pathology, Keio University Hospital, 35 Shinanomachi, Shinjuku-ku, 1608582, Tokyo, Japan;Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, 1608582, Tokyo, Japan;Division of Surgery, Department of Surgical Subspecialities, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 1578535, Japan;

关键词: Li-Fraumeni syndrome (LFS);    cancer stem cells (CSCs);    CD44 variant isoforms;   

DOI  :  10.1186/1471-2407-12-444

 received in 2012-07-15, accepted in 2012-09-27,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundLi-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome that is commonly associated with a germline mutation in the tumor suppressor gene p53. Loss of p53 results in increased expression of CD44, a cancer stem cell (CSC) marker, which is involved in the scavenging of reactive oxygen species (ROS). Here, we report a change in the expression of a CD44 variant isoform (CD44v8-10) in an 8-year-old female LFS patient with osteosarcoma and atypical liver cancer after chemotherapy.Case presentationThe patient visited a clinic with a chief complaint of chronic pain in a bruise on her right knee. Magnetic resonance imaging (MRI) raised the possibility of a bone malignancy. Biochemical testing also revealed significantly elevated levels of AFP, which strongly suggested the existence of a primary malignancy in the liver. MRI imaging showed the simultaneous development of osteosarcoma and liver cancer, both of which were confirmed upon biopsy. Combined therapy with surgical resection after chemotherapy was successful in this patient. Regardless of the absence of a familial history of hereditary cancer, a germline mutation in p53 was identified (a missense mutation defined as c.722 C>T, p.Ser241Phe). To better understand the cancer progression and response to treatment, immunohistochemical (IHC) analysis of biopsy specimens obtained before and after chemotherapy was performed using a specific antibody against CD44v8-10.ConclusionThis case demonstrates the ectopic up-regulation of CD44v8-10 in a biopsy sample obtained after cytotoxic chemotherapy, which confers high levels of oxidative stress on cancer cells. Because the alternative splicing of CD44 is tightly regulated epigenetically, it is possible that micro-environmental stress resulting from chemotherapy caused the ectopic induction of CD44v8-10 in vivo.

【 授权许可】

Unknown   
© Yoshida et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.