Expression Profiling in Soft Tissue Sarcomas With Emphasis
on Synovial Sarcoma, Gastrointestinal Stromal Tumor,
Robert B. West, MD, PhD
Abstract: Sarcomas are defined as malignant neoplasms derived
from mesenchymal tissues. A variety of different molecular
approaches, including gene expression profiling, have identified
candidate biomarkers and insights into sarcoma biology that will
aid in the diagnosis and treatment of these tumors. Many gene
expression profiling findings have been translated into immunohis-
tochemical tests for diagnostic, prognostic, or predictive purposes.
This review details gene expression studies done in 3 sarcomas,
synovial sarcoma, gastrointestinal stromal tumor, and leiomyo-
Key Words: synovial sarcoma, gastrointestinal stromal tumor,
leiomyosarcoma, sarcoma, soft tissue tumor, gene expression
profiling, microarray, RNA-seq
(Adv Anat Pathol 2010;17:366–373)
implications of the term malignancy are becoming blurred
as the number of clinical options for intervention and
follow-up increase and the term soft tissue tumors may be
more inclusive. These tumors are thought to be derived
from mesenchymal tissues including muscle, fat, nerves,
and other connective tissues. However, the true cell of
origin most likely represents a primitive, undifferentiated
cell with varying degrees of pluripotency. These concepts
are still poorly defined. Moreover, it is likely that certain
pathognomic genetic events can only result in neoplasia if
they occur in the correct stem cell type.1
Sarcomas can be broadly classified into groups based
on their genomic complexity and our knowledge to date.2
There are a number of diagnostic entities for which known
pathognomic molecular events such as translocations
and gene mutations have been described. The number of
diagnostic entities in this category is quite large, perhaps
larger than in any other cancer type, and can represent a
morphologic diagnostic challenge for pathologists. This is
especially daunting if the pathologist does not have access
to the newer diagnostic approaches such as fluorescence
in situ hybridization, in some instances, to confirm the
arcomas are defined as malignant neoplasms derived
from mesenchymal tissues. However, the criteria and
A variety of different molecular approaches, including
gene expression profiling, have identified candidate biomar-
kers and generated insights into sarcoma biology that will
aid in the diagnosis and treatment of these tumors. These
new biomarkers may act as surrogate markers for genomic
features and yet require simpler methodology that most
laboratories have access to, like immunohistochemistry.
The most common sarcomas, however, are not included
in the group that can be described by translocations and gene
mutations. Rather, the most common sarcomas have
complex karyotypes and pleomorphic histology and lack
identifiable molecular events. The least progress in sarcoma
research has been made in these tumors. Although it is
tempting to declare that these tumors are poorly differ-
entiated or undifferentiated representations of tumors with
no conserved molecular and morphologic features, there is
little evidence to suggest that this is the case. It is possible
that this group of sarcomas is analogous to the more
common carcinomas in terms of both genomic and
phenotypic complexity. This comparison gives us hope.
Considerable research effort has demonstrated that a
number of carcinomas, such as breast, can be classified
into different groups based on gene expression and DNA
copy number profiles. Moreover, these new groupings have
clinical pathologic correlations that can impact patient
care.3The difference in progress between the poorly defined
sarcomas and carcinomas may in part be due to the
differences in project design. The difference in specimen
numbers between sarcoma and carcinoma projects can
often be between 5 and 10 folds. This difference in power
dramatically affects the ability of a study to identify distinct
subgroups and, by extension, recurrent alterations at the
molecular level. Although these differences are bad enough,
there is an additional complexity in that most carcinoma
studies are restricted to a single organ system whereas most
of the sarcoma studies, being challenged for specimen
accrual, involve sarcomas from a wide variety of anatomic
locations that may not be biologically related.
Because of the mixture of tumors with pathognomic
molecular events, tumors that are as yet undefined, and
emerging pharmaceuticals that can target specific gene events,
it is an exciting time in the field of soft tissue tumor clinical
research (‘‘translational research’’). Larger, more sophisti-
cated expression profiling studies should continue to make
clinically relevant observations in sarcomas. Discoveries in
the biology of these tumors4,5can be quickly translated into
new and effective therapies. All these occur in the backdrop
of traditional treatment options including surgery, chemo-
therapy, and radiotherapy, which are improving as well,
especially as it is increasingly recognized that a comprehen-
sive multimodality approach can be very effective.
Copyrightr2010 by Lippincott Williams & Wilkins
From the Department of Pathology, Stanford University Medical
Center, Stanford, CA.
The author has no conflict of interest in this work.
Reprints: Robert B. West, MD, PhD, Department of Pathology,
Stanford University Medical Center, Room L235, 300 Pasteur
Drive, Stanford, CA 94305 (e-mail: firstname.lastname@example.org).
366|www.anatomicpathology.com Adv Anat Pathol?Volume 17, Number 5, September 2010
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Adv Anat Pathol?Volume 17, Number 5, September 2010 Expression Profiling in Soft Tissue Sarcomas
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