Outcome of patients with osteosarcoma over 40 years of age: is angiogenesis a marker of survival?
BACKGROUND
Osteosarcoma predominantly afflicts young people in their second and third decades of life. When osteosarcoma arises in patients older than 40 years, the prognosis is usually poorer compared to their younger counterparts. Although the clinical, histopathologic features and prognostic indicators are well defined for young patients, much less is known about affected adults. The purpose of this study is to describe our institution's experience with the management of osteosarcoma in patients greater than 40 years and also evaluate, by immunohistochemical analysis, the prognostic significance of microvessel density, as a marker of intratumoural angiogenesis.


METHODS
A retrospective clinicopathological analysis was performed on 11 patients over the age of 40 years that were treated at our institution between 1996 and 2004. Archival pre-treatment biopsy tissue was retrieved for immunohistochemical staining against two endothelial cell markers (CD31 and CD34) and also against VEGF. Angiogenesis was assessed by determining the intratumoural microvessel density (MVD) and the degree of VEGF expression in these specimens. This was correlated with patient outcome in terms of local recurrence, metastasis and death. Histological results were also compared to a group of patients less than 40 years of age.


RESULTS
Of the 11 patients, 9 were male and 2 were female and the mean age was 58 years (range, 42-85). In 7 patients, osteosarcoma arose secondarily from Paget's disease of the bone. The most common site involved was the humerus (7) followed by the femur (2) then pelvis (1) and ulna (1). At the time of diagnosis, 4 patients had metastatic disease. Preoperative chemotherapy was given to 4 patients, with a good response in 3 patients. Six patients underwent limb-sparing surgery, 4 had amputations and 1 was treated with radiotherapy alone. The mean follow up time was 31.5 months (range, 8-81). At this time, 4 patients (36%) had developed lung metastases and 5 patients (46%) had died. Overall survival was 54.5%. Intratumoural MVD was higher in patients over 40 years, although not statistically significant (p = 0.111, CD31; p = 0.134, CD34). VEGF was uniformly expressed in all sections, however no relationship was found between the degree of expression and patient age.


CONCLUSIONS
The prognosis for older patients with osteosarcoma is generally poor. Initial presentation is commonly associated with metastatic disease and neoadjuvant chemotherapy is often avoided because of its side effects. Increased intratumoural vascularity may contribute to the poorer prognosis in these patients, however further studies are needed.
Department of Orthopaedics, University of Melbourne, St. Vincent's Hospital, Melbourne, Australia. eugene_ek@msn.com
Eugene T H
ET
Ek
Joseline
J
Ojaimi
Yasuyuki
Y
Kitagawa
Peter F M
PF
Choong