PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of bmccancBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Cancer
 
BMC Cancer. 2012; 12: 444.
Published online Oct 2, 2012. doi:  10.1186/1471-2407-12-444
PMCID: PMC3488581
Li-Fraumeni syndrome with simultaneous osteosarcoma and liver cancer: Increased expression of a CD44 variant isoform after chemotherapy
Go J Yoshida,1 Yasushi Fuchimoto,corresponding author2 Tomoo Osumi,3 Hiroyuki Shimada,3 Seiichi Hosaka,4 Hideo Morioka,4 Makio Mukai,5 Yohei Masugi,6 Michiie Sakamoto,6 and Tatsuo Kuroda7
1Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 1608582, Japan
2Division of Surgery, Department of Surgical Subspecialities, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 1578535, Japan
3Department of Pediatrics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 1608582, Japan
4Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Japan
5Division of Diagnostic Pathology, Keio University Hospital, 35 Shinanomachi, Shinjuku-ku, Tokyo, 1608582, Japan
6Department of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 1608582, Japan
7Department of Pediatric Surgey, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 1608582, Japan
corresponding authorCorresponding author.
Go J Yoshida: go-21/at/lily.ocn.ne.jp; Yasushi Fuchimoto: yfuchimoto/at/z5.keio.jp; Tomoo Osumi: tomo-irie/at/sa3.so-net.ne.jp; Hiroyuki Shimada: hshimada/at/a5.keio.jp; Seiichi Hosaka: s.hosaka/at/scchr.jp; Hideo Morioka: morioka/at/z3.keio.jp; Makio Mukai: mukai/at/a2.keio.jp; Yohei Masugi: masugi/at/z6.keio.jp; Michiie Sakamoto: msakamot/at/z5.keio.jp; Tatsuo Kuroda: kuroda-t/at/z8.keio.jp
Received July 15, 2012; Accepted September 27, 2012.
Abstract
Background
Li-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 presentation
The 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.
Conclusion
This 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.
Keywords: Li-Fraumeni syndrome (LFS), cancer stem cells (CSCs), CD44 variant isoforms
Articles from BMC Cancer are provided here courtesy of
BioMed Central