Molecular prognosticators of complex karyotype soft tissue sarcoma outcome: a tissue microarray-based study.
BACKGROUND
Molecular markers are currently being utilized as sensitive prognosticators of cancer patient outcome. We sought to identify prognostic biomarkers for complex karyotype soft tissue sarcoma (STS).


METHODS
A large (n = 205) clinically annotated tissue microarray (TMA) was constructed and immunostained for several tumor-related markers. Staining was scored via an automated Ariol image analysis system; data were statistically analyzed to evaluate the correlation of clinicopathological and molecular variables with overall survival (OS) and local recurrence.


RESULTS
Multivariable analysis identified older age [hazard ratio (HR) 1.62, P < 0.0001], nonextremity location (HR 2.95, P = 0.001), high tumor grade (HR 2.5, P = 0.02), and increased matrix metalloproteinase (MMP) 2 expression (HR 1.74, P = 0.04) as predictors for poor OS. Similarly, older age (HR 1.51, P = 0.008), nonextremity location (HR 4.09, P = 0.001), and increased MMP2 expression (HR 6.28, P = 0.006) were all found to correlate with shorter local recurrence-free interval. High nuclear p53 expression was associated with shorter STS local recurrence-free interval, with a trend toward significance.


CONCLUSIONS
Data presented indicate that a clinically annotated TMA can be utilized to identify STS-related prognostic markers. Specifically, MMP2 and nuclear p53 should be further evaluated for their potential inclusion in complex karyotype STS staging systems.
Lahat
G
G
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Tuvin
D
D
Wei
C
C
Wang
W L
WL
Pollock
R E
RE
Anaya
D A
DA
Bekele
B N
BN
Corely
L
L
Lazar
A J
AJ
Pisters
P W
PW
Lev
D
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007621:Karyotyping; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D011446:Prospective Studies; D012509:Sarcoma / Q000175:diagnosis / Q000378:metabolism*; D015996:Survival Rate; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2