Utility of CD117 Immunoreactivity in Differentiating Metastatic Melanoma From Clear Cell Sarcoma

Abstract Context.—Clear cell sarcoma is a malignant soft tissue tumor with melanocytic differentiation. Molecular methods are sometimes necessary to identify the unique t(12; 22)(q13;q12) translocation and differentiate clear cell sarcoma from melanoma. Objective.—To determine whether CD117 immunoreactivity may be useful in separating melanoma from clear cell sarcoma. Design.—We identified 20 tumors listed in our surgical pathology files that were diagnosed as clear cell sarcoma or in which clear cell sarcoma was strongly considered. These were tested for the presence of the t(12;22) translocation by reverse transcriptase/polymerase chain reaction and sequencing from paraffin-embedded tissue. Tumors with a t(12;22) translocation were immunostained with an antibody to CD117 and compared with 16 similarly stained metastatic melanomas. Results.—Twelve tumors from 9 patients demonstrated t(12;22). No metastatic melanomas demonstrated t(12;22). None of the 12 clear cell sarcomas showed membrane or cytoplasmic staining for CD117. Conversely, 10 (63%) of 16 metastatic melanomas were, at least focally, positive for CD117; this difference was significant (P < .001). Interestingly, 3 tumors in which clear cell sarcoma was initially considered as a diagnosis, but which lacked t(12;22), were also positive for CD117. Conclusions.—Reverse transcriptase/polymerase chain reaction, performed on paraffin-embedded tissue, is a useful, rapid tool for identifying the presence of t(12;22) in clear cell sarcoma. The CD117 immunoreactivity may prove useful in the differential diagnosis of deep soft tissue or visceral lesions with melanocytic differentiation; positive staining results exclude clear cell sarcoma, but are compatible with metastatic melanoma.

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Diagnosis of clear cell sarcoma by real-time reverse transcriptase-polymerase chain reaction analysis of paraffin embedded tissues

Cancer ◽

10.1002/cncr.22099 ◽

2006 ◽

Vol 107 (5) ◽

pp. 1055-1064 ◽

Cited By ~ 63

Author(s):

Jean-Michel Coindre ◽

Isabelle Hostein ◽

Philippe Terrier ◽

Corinne Bouvier-Labit ◽

Francoise Collin ◽

...

Keyword(s):

Polymerase Chain Reaction ◽

Reverse Transcriptase ◽

Real Time ◽

Clear Cell ◽

Clear Cell Sarcoma ◽

Polymerase Chain Reaction Analysis ◽

Chain Reaction ◽

Cell Sarcoma ◽

Polymerase Chain

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Clear cell sarcoma of soft tissue: diagnostic utility of fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction

Journal of Cutaneous Pathology ◽

10.1111/j.1600-0560.2007.00821.x ◽

2008 ◽

Vol 35 (4) ◽

pp. 411-417 ◽

Cited By ~ 14

Author(s):

Choladda V. Curry ◽

Megan K. Dishop ◽

M. John Hicks ◽

Rizwan Naeem ◽

Jon A. Reed ◽

...

Keyword(s):

Polymerase Chain Reaction ◽

In Situ Hybridization ◽

Soft Tissue ◽

Clear Cell ◽

Clear Cell Sarcoma ◽

Diagnostic Utility ◽

Chain Reaction ◽

Cell Sarcoma ◽

Polymerase Chain

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Diagnotic Significance of Detection of Fusion Genes by Reverse Transcriptase-Polymerase Chain Reaction in Soft Tissue Tumors

Orthopedics & Traumatology ◽

10.5035/nishiseisai.58.473 ◽

2009 ◽

Vol 58 (3) ◽

pp. 473-477

Author(s):

Kensaku Yamaga ◽

Hideki Yamashita ◽

Koji Endo ◽

Mitsuhiko Osaki ◽

Takeshi Minamizaki ◽

...

Keyword(s):

Polymerase Chain Reaction ◽

Soft Tissue ◽

Reverse Transcriptase ◽

Soft Tissue Tumors ◽

Fusion Genes ◽

Chain Reaction ◽

Polymerase Chain

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Clear cell sarcoma of tendons and aponeuroses, and osteoclast-rich tumour of the gastrointestinal tract with features resembling clear cell sarcoma of soft parts: a review and update

Journal of Clinical Pathology ◽

10.1136/jcp.2008.057471 ◽

2010 ◽

Vol 63 (5) ◽

pp. 416-423 ◽

Cited By ~ 72

Author(s):

Kemal Kosemehmetoglu ◽

Andrew L Folpe

Keyword(s):

Gastrointestinal Tract ◽

Young Adult ◽

Malignant Melanoma ◽

Soft Tissue ◽

Clear Cell ◽

Clear Cell Sarcoma ◽

Soft Tissue Neoplasm ◽

Cell Sarcoma ◽

Melanocytic Differentiation ◽

Gastrointestinal Neoplasm

Clear cell sarcoma (CCS) is a rare, distinctive soft tissue neoplasm, typically occurring in the distal extremities of young adult patients. Although CCS shows melanocytic differentiation, it is now clear that it is clinicopathologically and genetically distinct from conventional malignant melanoma. The ‘osteoclast-rich tumour of the gastrointestinal tract with features resembling clear cell sarcoma of soft parts’ is an extraordinarily rare gastrointestinal neoplasm that shares some features of CCS, but differs from it in other ways. The historical, histopathological, ultrastructural, immunohistochemical and genetic aspects of these two tumours are reviewed in this article.

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Prognostic Value of Tyrosinase Reverse-Transcriptase Polymerase Chain Reaction in Metastatic Melanoma

Dermatology ◽

10.1159/000051753 ◽

2001 ◽

Vol 203 (3) ◽

pp. 221-225 ◽

Cited By ~ 7

Author(s):

G. Quereux ◽

M. Denis ◽

A. Khammari ◽

P. Lustenberger ◽

B. Dreno

Keyword(s):

Polymerase Chain Reaction ◽

Reverse Transcriptase ◽

Metastatic Melanoma ◽

Prognostic Value ◽

Chain Reaction ◽

Polymerase Chain

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c-kit Is Expressed in Soft Tissue Sarcoma of Neuroectodermic Origin and Its Ligand Prevents Apoptosis of Neoplastic Cells

Blood ◽

10.1182/blood.v91.7.2397 ◽

1998 ◽

Vol 91 (7) ◽

pp. 2397-2405 ◽

Cited By ~ 67

Author(s):

Emanuela Ricotti ◽

Franca Fagioli ◽

Emanuela Garelli ◽

Claudia Linari ◽

Nicoletta Crescenzio ◽

...

Keyword(s):

Polymerase Chain Reaction ◽

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Reverse Transcriptase ◽

Cell Lines ◽

Enzyme Linked Immunosorbent Assay ◽

Thymidine Uptake ◽

Chain Reaction ◽

Functional Block ◽

Polymerase Chain

Abstract During development, mice with mutations of stem cell factor (SCF) or its receptor c-kit exhibit defects in melanogenesis, as well as hematopoiesis and gonadogenesis. Consequently, accumulating evidence suggests that the c-kit/SCF system plays a crucial role in all of these processes and in tumors which derive from them. Especially in neuroblastoma (infant tumors of neuroectoderm crest derivation such as melanocytes) it would appear that an autocrine loop exists between c-kit and SCF, and that the functional block of the c-kit receptors with monoclonal antibodies (MoAbs) results in a significant decrease in cellular proliferation. We studied the expression and role of c-kit and SCF in cell lines of soft tissue sarcoma of neuroectodermic origin, such as Ewing's sarcoma (ES) and peripheral neuro-ectodermal tumors (PNET). Using flow cytometry with MoAb CD117 PE, c-kit expression was highlighted in all six of the cell lines examined. This receptor was specifically and functionally activated by SCF, as shown by the binding experiments and the intracellular phosphotyrosine and immunoprecipitation studies that were performed. Using reverse transcriptase polymerase chain reaction analysis, five of the six cellular lines expressed the mRNA of SCF. In the medium measured by using an enzyme- linked immunosorbent assay, low concentrations of SCF were found: only the TC32 cellular line produced significantly higher levels (32 pg) than control. In serum-free culture the addition of SCF reduced the percentage of apoptotic cells from 25% to 90% in five out of the six cellular lines. This observation was confirmed by (1) the functional block of c-kit with MoAb: after 7 days of culture more than 30% of the cells were apoptotic (range 31.5% to 100%) in five out of six cell lines and there was also a decrease in the percentage of cells in phase S, and (2) c-kitantisense oligonucleotides: in the cellular lines treated with oligonucleotides (in relation to the untreated lines) there was a notable reduction (P < .001) both in the absolute number of cells and the 3H-thymidine uptake. These results indicate that ES and PNET express c-kit and its ligand SCF and that SCF is capable of protecting the tumor cells against apoptosis. Furthermore, the reverse transcriptase–polymerase chain reaction performed on the biopsies revealed the presence of mRNA both of SCF and c-kit in practically all of the samples studied. Our in vitro data lead us to assume that SCF may also inhibit tumor cell apoptosis in vivo.

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c-kit Is Expressed in Soft Tissue Sarcoma of Neuroectodermic Origin and Its Ligand Prevents Apoptosis of Neoplastic Cells

Blood ◽

10.1182/blood.v91.7.2397.2397_2397_2405 ◽

1998 ◽

Vol 91 (7) ◽

pp. 2397-2405 ◽

Cited By ~ 3

Author(s):

Emanuela Ricotti ◽

Franca Fagioli ◽

Emanuela Garelli ◽

Claudia Linari ◽

Nicoletta Crescenzio ◽

...

Keyword(s):

Polymerase Chain Reaction ◽

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Reverse Transcriptase ◽

Cell Lines ◽

Enzyme Linked Immunosorbent Assay ◽

Thymidine Uptake ◽

Chain Reaction ◽

Functional Block ◽

Polymerase Chain

During development, mice with mutations of stem cell factor (SCF) or its receptor c-kit exhibit defects in melanogenesis, as well as hematopoiesis and gonadogenesis. Consequently, accumulating evidence suggests that the c-kit/SCF system plays a crucial role in all of these processes and in tumors which derive from them. Especially in neuroblastoma (infant tumors of neuroectoderm crest derivation such as melanocytes) it would appear that an autocrine loop exists between c-kit and SCF, and that the functional block of the c-kit receptors with monoclonal antibodies (MoAbs) results in a significant decrease in cellular proliferation. We studied the expression and role of c-kit and SCF in cell lines of soft tissue sarcoma of neuroectodermic origin, such as Ewing's sarcoma (ES) and peripheral neuro-ectodermal tumors (PNET). Using flow cytometry with MoAb CD117 PE, c-kit expression was highlighted in all six of the cell lines examined. This receptor was specifically and functionally activated by SCF, as shown by the binding experiments and the intracellular phosphotyrosine and immunoprecipitation studies that were performed. Using reverse transcriptase polymerase chain reaction analysis, five of the six cellular lines expressed the mRNA of SCF. In the medium measured by using an enzyme- linked immunosorbent assay, low concentrations of SCF were found: only the TC32 cellular line produced significantly higher levels (32 pg) than control. In serum-free culture the addition of SCF reduced the percentage of apoptotic cells from 25% to 90% in five out of the six cellular lines. This observation was confirmed by (1) the functional block of c-kit with MoAb: after 7 days of culture more than 30% of the cells were apoptotic (range 31.5% to 100%) in five out of six cell lines and there was also a decrease in the percentage of cells in phase S, and (2) c-kitantisense oligonucleotides: in the cellular lines treated with oligonucleotides (in relation to the untreated lines) there was a notable reduction (P < .001) both in the absolute number of cells and the 3H-thymidine uptake. These results indicate that ES and PNET express c-kit and its ligand SCF and that SCF is capable of protecting the tumor cells against apoptosis. Furthermore, the reverse transcriptase–polymerase chain reaction performed on the biopsies revealed the presence of mRNA both of SCF and c-kit in practically all of the samples studied. Our in vitro data lead us to assume that SCF may also inhibit tumor cell apoptosis in vivo.

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