VOL. 94-B, No. 3, MARCH 2012 419 ONCOLOGY A preliminary investigation of Beta-hCG expression in patients with osteosarcoma K. Z. Masrouha, R. Khattab, A. Tawil, A. Abdallah, S. Saghieh, R. Haidar, M. Abboud, N. J. Khoury From American University of Beirut Medical Center, Beirut, Lebanon K. Z. Masrouha, MD, Resident S. Saghieh, MD, Associate Professor of Clinical Orthopaedic Surgery R. Haidar, MD, Professor of Clinical Orthopaedic Surgery American University of Beirut Medical Center, Division of Orthopaedic Surgery, P.O. Box 11-0236, Riad El-Solh, Beirut 1107 2020, Lebanon. R. Khattab, MD, Resident A. Tawil, MD, Professor of Clinical Pathology American University of Beirut Medical Center, Department of Pathology and Laboratory Medicine, P.O. Box 11-0236, Riad El-Solh, Beirut 1107 2020, Lebanon. A. Abdallah, MD, Resident M. Abboud, MD, Professor of Pediatric Hematology/ Oncology American University of Beirut Medical Center, Department of Pediatrics and Adolescent Medicine, P.O. Box 11-0236, Riad El-Solh, Beirut 1107 2020, Lebanon. N. J. Khoury, MD , Associate Professor of Clinical Radiology American University of Beirut Medical Center, Department of Diagnostic Radiology, P.O. Box 11-0236, Riad El-Solh, Beirut 1107 2020, Lebanon. Correspondence should be sent to Dr N. J. Khoury; e-mail: nk01@aub.edu.lb ©2012 British Editorial Society of Bone and Joint Surgery doi:10.1302/0301-620X.94B3. 27679 $2.00 J Bone Joint Surg Br 2012;94-B:419–24. Received 31 May 2011; Accepted after revision 17 November 2011 There are eight reported cases in the literature of osteosarcomas secreting β-hCG. Our primary aim was to investigate the rate of β-hCG expression in osteosarcoma and attempt to understand the characteristics of osteosarcomas that secrete β-hCG. We reviewed 37 histopathology slides (14 biopsies and 23 surgical specimens) from 32 patients with osteosarcoma. The slides were retrospectively stained for β-hCG expression. Patient and tumour characteristics, including age, gender, tumour location, subtype, proportion of necrosis, presence of metastases and recurrence were recorded. A total of five of the 32 tumours were found to be positive for β-hCG expression (one strongly and four weakly). This incidence of this expression was found in tumours with poor histological response to neoadjuvant chemotherapy. The use of β-hCG expression as a diagnostic, prognostic or follow-up marker is questionable and needs further investigation with a larger sample size. Human chorionic gonadotropin (hCG) is a glycoprotein which is usually produced by the placental syncytiotrophoblasts in healthy preg- nant women from six to eight days after con- ception. 1 It is composed of two subunits which are non-covalently linked: alpha and beta. The alpha subunit is biochemically similar to pituitary gonadotropins (follicle-stimulating hormone (FSH) and luteinizing hormone (LH)) and thyroid stimulating hormone (TSH), mak- ing it non-specific and of little use as a tumour marker. On the other hand, the beta (β) subu- nit, which is 80% homologous, has strong specificity and is used to diagnose pregnancy and many obstetric and gynaecological disorders including hydatiform moles, chorio- carcinoma and ovarian neoplasms. 1 In addi- tion, β-hCG may be produced by non- gynaecological organs, including the testes, 2 , colon, 1 liver, 1 lungs, 1,3 stomach, 1 bone 1,3-8 and breast. 9 Therefore, increased blood levels might be found in patients with tumours aris- ing from these organs, particularly of the testes, bladder, and pancreas. 4,7 There are only eight patients reported in the literature with a diagnosis of osteosarcoma who were found to have immunohistochemical proof of β-hCG expression. 1,3-8 In six of these there were elevated serum levels of β-hCG. 1,4-8 Reports suggest the potential use of this glyco- protein as both a prognostic and follow-up marker in patients with osteosarcoma. 3,6 How- ever, this has not been extensively studied in these patients. If a correlation is established between β-hCG expression and osteosarcoma, it might serve as a useful tool in the manage- ment of these patients. We present the results of immunohistochem- ical staining for β-hCG expression in histology slides from patients with osteosarcoma to assess the incidence of β-hCG positivity. Patients and Methods After obtaining Institutional Review Board approval we retrospectively reviewed histology slides from patients with osteosarcoma treated at the Children’s Cancer Center of Lebanon, between 2002 and 2010. Initially, 37 cases of osteosarcoma were retrieved. The studied tumour tissues were originally fixed with for- malin for four to six hours for open biopsy and 24 hours for excision biopsy specimens. These were then decalcified using a solution of hydrochloride and acetic acids (Surgipath Decalcifier II; Leica Biosystems, Richmond, Illinois) for a period of three to four hours for open biopsy and 12 to 24 hours for excisional biopsy specimens. The haematoxylin and eosin-stained sectioned slides were reviewed by an attending pathologist (AT) and a pathology resident (RK), taken from all available speci- mens, whether open biopsy at the time of diag- nosis and/or excised tumour. The slides of all tumours were reviewed to select appropriate blocks. For each patient, the slide that demon- strated the greatest proportion of viable