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Other useful IHC markers in identifying soft tissue tumors:� Type IV Collagen: While not specific for a cell or tumor type, the presence and even pattern of expression of type IV
collagen can be helpful in identifying specific soft tissue tumor subtypes, as only a subset of sarcomas produce a type IV
collagen; furthermore, the pattern of type IV collagen expression can provide evidence to help identify selected spindle cell
tumors.
����������� is normally a cell membrane-associated protein. However, alterations in the APC/beta catenin pathway result
in abnormal nuclear localization of this protein. Only a restricted subset of spindle cell tumors, including fibromatoses,
endometrial stromal tumors, solitary fibrous tumors, and synovial sarcomas, show this unique distribution of beta catenin.
� DOG1 and CD117 (c-kit) are highly sensitive and specific markers for gastrointestinal stromal tumors. DOG1 is
particularly useful in identifying the subset of c-kit negative gastrointestinal stromal tumors (GISTs).
���� � is a marker of a unique subset of spindle cell tumors. In addition to vascular tumors, CD34 is expressed in
dermatofibrosarcoma protuberans, solitary fibrous tumor/hemangiopericytoma, and a subset of nerve sheath tumors,
among others.
������� is a highly sensitive and specific marker for synovial sarcoma. This protein, initially identified with gene expression
profiling, is best used as a ‘screening marker’ for synovial sarcoma and, if positive, followed by confirmatory FISH for the
SYT translocation. Other spindle cell tumors may occasionally show high-level expression of TLE-1 such as peripheral
nerve sheath tumors.
������� is a tumor supressor gene product, the loss of which has been found to be a characteristic finding of the following
tumors: rhabdoid tumors, atypical teratoid/ rhabdoid tumors of the CNS, epithelioid sarcoma, MPNST, myxoid
chondrosarcoma, and soft tissue myoepitheliomas.
������� is the glycoprotein to which the monoclonal antibody HMB-45 is directed. In addition to being a marker of
melanoma and clear cell sarcoma, gp100 expression also characterizes the group of tumors known as PEComas (PEC =
perivascular epithelioid cell), a family of spindle to epithelioid tumors that includes angiomyolipoma, sugar tumor of the
lung, pulmonary lymphangioleiomyomatosis, clear cell myomelanocytic tumor of the falciform ligamentum teres, and
others.
TLE-1Synovial sarcoma showing uniform expression of the nuclear protein, TLE-1.
Beta cateninNuclear localization of beta catenin is a characteristic feature of the cells of abdominal fibromatosis.
CD117 (c-kit)Strong uniform expression of c-kit in a case of gastrointestinal stromal tumor.
Chromosomal TranslocationsApproximately one-third of all sarcomas contain chromosomal translocations which result in the juxtapositioning of two different
genes (one from each translocation partner) that form a ‘fusion gene’. An example is the EWSR-WT1 fusion which results from the
t(11;22)(p13;q12) translocation found in desmoplasic small round cell tumor. For detection of these translocations in tissue sections
of the tumor, two different types of probes or probe sets can be employed: (a) dual fusion, dual color FISH probes, which identify the
chromosomes participating in the translocation; a ‘positive’ result is one in which normally disparate red and green signals ‘fuse’ as a
result of the translocation into a single yellow spot; (b) breakapart probes, in which two different-colored probes span the expected
breakpoint region in one of the partner genes, with a ‘positive’ result yielding disparate (e.g., red and green) spots that would normally
be a single yellow spot.
FISH for SYT translocations of synovial sarcoma: The histologic diagnosis of synovial sarcoma can be difficult as these
tumors often resemble other spindle cell sarcomas. IHC studies are usually helpful in characterizing these tumors, but many of the
marker studies (TLE-1 and beta catenin) used to confirm this diagnosis are not completely specific. Translocations involving the SYT
gene on chromosome 18q11.2 are unique to, and ultimately define, synovial sarcomas, and confirmation of this diagnosis can be made
with high sensitivity and specificity using dual color, ‘breakapart’ FISH studies. In these assays, translocations involving the SYT gene
lead to a breakapart of the normal red-(yellow)-green overlapping signal, resulting in distinct red and green signals, as illustrated below,
which confirm the presence of the SYT translocation characteristic of synovial sarcoma.
FISH for translocations of the SYT gene characteristic of synovial sarcoma