The expression of c-Met pathway components in unclassified pleomorphic sarcoma/malignant fibrous histiocytoma (UPS/MFH): a tissue microarray study.
OBJECTIVE
Subclassification of undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma (UPS/MFH) into distinct biological cohorts based on the expression patterns of molecular markers can identify patient subsets with especially unfavourable clinical outcomes. Identification of molecular prognosticators amenable for drug targeting can facilitate rational development of UPS/MFH tailored therapies. The aim was to evaluate expression of c-Met pathway components in a large cohort of UPS/MFH samples.


RESULTS
An immunohistochemical analysis for hepatocyte growth factor (HGF), c-Met, phospho-c-Met (pc-Met), phospho-mitogen-activated protein kinase kinase (MAPKK) also known as mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (p-MEK) and phospho-protein kinase B (p-AKT) was performed on a clinically annotated tissue microarray of 158 UPS/MFH samples. Univariable and multivariable analyses were conducted to evaluate the correlation of molecular variables with UPS/MFH disease specific survival. All evaluated markers were expressed in UPS/MFH to varying levels. Most importantly, strong HGF, pc-Met, p-MEK and p-AKT expression correlated significantly with dismal patient outcome on univariable statistical analysis. Expression of p-MEK and p-AKT remained statistically significant independent prognosticators on multivariable analysis.


CONCLUSIONS
c-Met pathway components and especially p-MEK and p-AKT are potential prognostic biomarkers for UPS/MFH; their inclusion in future molecular-based staging systems should be evaluated. Furthermore, novel approaches targeting HGF, c-Met, MEK/extracellular-regulated kinase (ERK) and/or AKT should be considered for a subset of UPS/MFH patients.
Department of Surgical Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030-4009, USA.
Guy
G
Lahat
Pingyu
P
Zhang
Quan-Sheng
QS
Zhu
Keila
K
Torres
Markus
M
Ghadimi
Kerrington D
KD
Smith
Wei-Lien
WL
Wang
Alexander J
AJ
Lazar
Dina
D
Lev
D014408:Biomarkers, Tumor / Q000032:analysis*; D051677:Histiocytoma, Malignant Fibrous / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D020930:MAP Kinase Kinase Kinases / Q000096:biosynthesis; D011379:Prognosis; D016016:Proportional Hazards Models; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis*; D012983:Soft Tissue Neoplasms / Q000378:metabolism* / Q000473:pathology; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D019859:Proto-Oncogene Proteins c-met; D051057:Proto-Oncogene Proteins c-akt; D020930:MAP Kinase Kinase Kinases