Validation of potential therapeutic targets in alveolar soft part sarcoma: an immunohistochemical study utilizing tissue microarray.
OBJECTIVE
The molecular signature of alveolar soft part sarcoma (ASPS) is a specific der(17)t(X;17)(p11.2;q25) translocation, resulting in a chimeric transcription factor (ASPSCR1-TFE3). When this disease is no longer amenable to surgical curative intervention, uniformly efficacious therapies are lacking. The aim of this study was to evaluate the expression of potential molecular therapeutic targets in a cohort of ASPS tumour samples.


RESULTS
Immunohistochemical analysis for hepatocyte growth factor, c-Met, phosphorylated c-Met, phosphorylated AKT, phosphorylated MEK, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), p53 and vimentin was performed on an ASPS tissue microarray, yielding complete data from 26 tumours. Activation of c-Met and its downstream effectors was noted, whereas only limited EGFR expression was seen. VEGF was expressed to varying degrees. Only one sample exhibited strong nuclear p53 expression, while 10 expressed low levels. Vimentin expression was negative in the vast majority of samples (96%).


CONCLUSIONS
There is a crucial need for better anti-ASPS therapies. Activated c-Met and the phosphorylation of its downstream effectors validate an intact signalling cascade probably induced by the ASPSCR1-TFE3 chimeric transcription factor. The angiogenic phenotype of these tumours is supported by increased angiogenic factor expression. Combination therapies targeting both tumour cells and angiogenesis merit further investigation.
Lazar
Alexander J
AJ
Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Sarcoma Research Center, Houston, TX 77030-4009, USA. alazar@mdanderson.com
Lahat
Guy
G
Myers
Sarah E
SE
Smith
Kerrington D
KD
Zou
Changye
C
Wang
Wei-Lien
WL
Lopez-Terrada
Dolores
D
Lev
Dina
D
D006801:Humans; D007150:Immunohistochemistry; D009363:Neoplasm Proteins / Q000378:metabolism*; D018234:Sarcoma, Alveolar Soft Part / Q000378:metabolism*; D012983:Soft Tissue Neoplasms / Q000378:metabolism*; D046888:Tissue Array Analysis
D009363:Neoplasm Proteins