Prognostic impact of adenomatous polyposis coli gene expression in osteosarcoma of the extremities.
OBJECTIVE
To evaluate the impact of adjuvant chemotherapy on the outcome of osteosarcoma of the extremities, and to identify prognostic factors using the expression of adenomatous polyposis coli (APC), cadherin and β-catenin Wnt-signalling markers.


METHODS
The clinical, demographic, anatomic and pathological factors including a detailed analysis of the immunohistochemical expression of cadherin, β-catenin and APC were retrospectively examined in 97 patients with osteosarcoma of the extremities (metastatic and non-metastatic at diagnosis), treated with surgery and/or chemotherapy from 1985 to 2000.


RESULTS
APC immunoreactivity showed a statistically significant association with age and serum alkaline phosphatase levels (p = 0.025 and p = 0.038). When survival was the end-point of multivariate analysis, race segregated patients with poor survival as did lack of cadherin expression. For overall survival, cadherin immunoreactivity and the interaction between APC expression and response to adjuvant chemotherapy were significant (p = 0.012 and p<0.001). No significant clinical association was evident with immunohistochemical expression of cadherin, β-catenin.


CONCLUSIONS
Lack of expression of cadherin was a significant variable to overall and disease-free survival. Significantly, positive APC immunoreactivity and adjuvant chemotherapy were associated with a favourable treatment response. Studies using newer immunohistochemical markers within the Wnt-signalling pathway may guide the development of more appropriate therapeutic targets for future individualised treatment.
Guimarães
Andréa Paiva Gadelha
AP
Department of Clinical Oncology, Cancer Hospital AC Camargo, Brazil.
Rocha
Rafael Malagoli
RM
da Cunha
Isabela Werneck
IW
Guimarães
Gustavo Cardoso
GC
Carvalho
André Lopes
AL
de Camargo
Beatriz
B
Lopes
Ademar
A
Squire
Jeremy Andrew
JA
Soares
Fernando Augusto
FA
D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000235:genetics* / Q000401:mortality; D015820:Cadherins / Q000378:metabolism; D002648:Child; D005121:Extremities; D005260:Female; D017491:Genes, APC; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012516:Osteosarcoma / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D012189:Retrospective Studies; D055815:Young Adult
D015820:Cadherins