Prognostic significance of immunohistochemical expression of ezrin in non-metastatic high-grade osteosarcoma.
BACKGROUND
Ezrin is a membrane-cytoskeleton linker protein involved in regulating growth and metastatic behaviour of cancer cells. The study evaluated ezrin expression and its prognostic value in patients with non-metastatic osteosarcoma.


METHODS
Ezrin expression and pattern of staining (cytoplasmic or membraneous and cytoplasmic) were assessed using immunohistochemistry on slides from tumour biopsy. We studied 95 patients (median 16 years, range: 4-39 years) with primary non-metastatic osteosarcoma of the extremity treated by neoadjuvant chemotherapy based on methotrexate, cisplatin, doxorubicin and ifosfamide.


RESULTS
Seventy-six patients (80%) showed ezrin immunoreactivity: in cytoplasm (37, 47%) and in cytoplasm and membrane (42, 53%) of tumour cells. Immunohistochemical staining score was: 1+ (16, 24%), 2+ (10, 13%), 3+ (17, 21.5%) and 4+ (36, 45.5%). Ezrin and score expression were not related to gender, site, alkaline phosphatase (AP), LDH serum levels, chemotherapy-induced tumour necrosis or patient outcome. A significant association was seen between expression pattern and prognosis. The 3-year probability of disease-free survival was 80% for patients with only cytoplasmic immunostaining and 54% for patients with cytoplasmic and membranous immunostaining (P < 0.02).


CONCLUSIONS
Ezrin immunoreactivity can be detected in the majority of patients with non-metastatic osteosarcoma of the extremity. The pattern of ezrin staining can identify patients with different risks of relapse. In patients who only have ezrin cytoplasmic expression, a probability of EFS >80% at 5 years can be expected. These results suggest further investigations to define the relation between expression pattern, ezrin functional status and outcome in patients with non-metastatic osteosarcoma.
Ferrari
Stefano
S
Chemotherapy Unit, Istituto Ortopedico Rizzoli, Bologna, Italy. stefano.ferrari@ior.it
Zanella
Licciana
L
Alberghini
Marco
M
Palmerini
Emanuela
E
Staals
Eric
E
Bacchini
Patrizia
P
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols; D014408:Biomarkers, Tumor / Q000032:analysis*; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003598:Cytoskeletal Proteins / Q000096:biosynthesis*; D018572:Disease-Free Survival; D005121:Extremities / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020360:Neoadjuvant Therapy; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D000099149:Ezrin
D014408:Biomarkers, Tumor; D003598:Cytoskeletal Proteins; D000099149:Ezrin