Expression of receptor tyrosine kinases epidermal growth factor receptor and HER-2/ neu in synovial sarcoma

Dafydd G. Thomas, Thomas J. Giordano, Donita Sanders, Sybil Biermann, Vernon K. Sondak, Jonathan Trent, Dihua Yu, Raphael E. Pollock, Laurence Baker

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

BACKGROUND. Synovial sarcomas are high-grade soft tissue neoplasms often characterized by a biphasic spindle and epithelioid cell morphology. The majority of synovial sarcomas harbor a specific chromosomal translocation in which the proximal portion of the SYT gene at chromosome 18q11 is fused to the distal portion of one of several duplicated SSX genes (most notably SSX1 and SSX2) at chromosome Xp11. SYT/SSX1 translocations are seen in nearly three times as many synovial sarcomas as SYT/SSX2 translocations. Although the SYT/SSX2 fusion is usually associated with the monophasic disease pattern, the SYT/SSX1 fusion is present in tumors with biphasic or monophasic patterns. The SYT/SSX1 fusion gene is associated with more aggressive tumor growth and poor outcome. Despite advances in the therapy of local disease, distant metastasis remains the predominant cause of death. Accordingly, there is a need for alternate therapies, such as those recently developed against the receptor tyrosine kinases, such as epidermal growth factor receptor (EGFR) and HER-2/ neu. METHODS. Archival specimens of synovial sarcoma (n = 38) representing 30 patients were assessed for EGFR and HER-2/ neu protein expression by standard immunohistochemical techniques. To validate the immunohistochemistry results, quantitative real-time polymerase chain reaction (Q-PCR) assays using either fresh and/or archival material was performed. The presence of gene amplification was determined by chromogenic in-situ hybridization. RESULTS. EGFR and HER-2/ neu protein were detected by immunohistochemistry in 21 of 38 (55.3%) and 20 of 38 (52.6%) synovial specimens, respectively. EGFR immunoreactivity showed a granular and membranous pattern, whereas HER-2/ neu immunoreactivity demonstrated only a membrane pattern. Coexpression was observed in 13 of 38 specimens (34.2%). HER-2/ neu expression by immunohistochemistry in synovial sarcomas was restricted to tumors with the SYT/SSX1 translocations. Of 6 specimens with SSX2 translocation, none (0%) showed HER-2/ neu immunoreactivity and 1 (17%) demonstrated EGFR expression. Q-PCR demonstrated the presence of mRNA for EGFR and HER-2/ neu in 19 of 30 specimens (63.3%) and 22 of 30 specimens (73.3%), respectively. EGFR and HER-2/ neu were expressed at low concentrations compared with the expression of glyceraldehyde 3-phosphate dehydrogenase (GAPDH). No evidence of gene amplification was observed. CONCLUSIONS. EGFR and HER-2/ neu are expressed in the majority of patients with SYT/SSX1 synovial sarcomas, albeit at low levels. Treatment with tyrosine kinase inhibitors may represent appropriate alternate therapy for these patients.

Original languageEnglish
Pages (from-to)830-838
Number of pages9
JournalCancer
Volume103
Issue number4
DOIs
StatePublished - Feb 15 2005
Externally publishedYes

Fingerprint

Synovial Sarcoma
Epidermal Growth Factor Receptor
Gene Amplification
Immunohistochemistry
Real-Time Polymerase Chain Reaction
Chromosomes
Soft Tissue Neoplasms
Epithelioid Cells
Neoplasms
Genetic Translocation
Glyceraldehyde-3-Phosphate Dehydrogenases
Gene Fusion
Receptor Protein-Tyrosine Kinases
Therapeutics
SYT-SSX fusion protein
Protein-Tyrosine Kinases
Genes
In Situ Hybridization
Cause of Death
Proteins

Keywords

  • Chromogenic in situ hybridization
  • Epidermal growth factor receptor
  • HER-2/ neu
  • Immunohistochemistry
  • Quantitative polymerase chain reaction
  • Synovial sarcoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Thomas, D. G., Giordano, T. J., Sanders, D., Biermann, S., Sondak, V. K., Trent, J., ... Baker, L. (2005). Expression of receptor tyrosine kinases epidermal growth factor receptor and HER-2/ neu in synovial sarcoma. Cancer, 103(4), 830-838. https://doi.org/10.1002/cncr.20847

Expression of receptor tyrosine kinases epidermal growth factor receptor and HER-2/ neu in synovial sarcoma. / Thomas, Dafydd G.; Giordano, Thomas J.; Sanders, Donita; Biermann, Sybil; Sondak, Vernon K.; Trent, Jonathan; Yu, Dihua; Pollock, Raphael E.; Baker, Laurence.

In: Cancer, Vol. 103, No. 4, 15.02.2005, p. 830-838.

Research output: Contribution to journalArticle

Thomas, DG, Giordano, TJ, Sanders, D, Biermann, S, Sondak, VK, Trent, J, Yu, D, Pollock, RE & Baker, L 2005, 'Expression of receptor tyrosine kinases epidermal growth factor receptor and HER-2/ neu in synovial sarcoma', Cancer, vol. 103, no. 4, pp. 830-838. https://doi.org/10.1002/cncr.20847
Thomas DG, Giordano TJ, Sanders D, Biermann S, Sondak VK, Trent J et al. Expression of receptor tyrosine kinases epidermal growth factor receptor and HER-2/ neu in synovial sarcoma. Cancer. 2005 Feb 15;103(4):830-838. https://doi.org/10.1002/cncr.20847
Thomas, Dafydd G. ; Giordano, Thomas J. ; Sanders, Donita ; Biermann, Sybil ; Sondak, Vernon K. ; Trent, Jonathan ; Yu, Dihua ; Pollock, Raphael E. ; Baker, Laurence. / Expression of receptor tyrosine kinases epidermal growth factor receptor and HER-2/ neu in synovial sarcoma. In: Cancer. 2005 ; Vol. 103, No. 4. pp. 830-838.
@article{c215a8a70c1744e8b1180add1094128a,
title = "Expression of receptor tyrosine kinases epidermal growth factor receptor and HER-2/ neu in synovial sarcoma",
abstract = "BACKGROUND. Synovial sarcomas are high-grade soft tissue neoplasms often characterized by a biphasic spindle and epithelioid cell morphology. The majority of synovial sarcomas harbor a specific chromosomal translocation in which the proximal portion of the SYT gene at chromosome 18q11 is fused to the distal portion of one of several duplicated SSX genes (most notably SSX1 and SSX2) at chromosome Xp11. SYT/SSX1 translocations are seen in nearly three times as many synovial sarcomas as SYT/SSX2 translocations. Although the SYT/SSX2 fusion is usually associated with the monophasic disease pattern, the SYT/SSX1 fusion is present in tumors with biphasic or monophasic patterns. The SYT/SSX1 fusion gene is associated with more aggressive tumor growth and poor outcome. Despite advances in the therapy of local disease, distant metastasis remains the predominant cause of death. Accordingly, there is a need for alternate therapies, such as those recently developed against the receptor tyrosine kinases, such as epidermal growth factor receptor (EGFR) and HER-2/ neu. METHODS. Archival specimens of synovial sarcoma (n = 38) representing 30 patients were assessed for EGFR and HER-2/ neu protein expression by standard immunohistochemical techniques. To validate the immunohistochemistry results, quantitative real-time polymerase chain reaction (Q-PCR) assays using either fresh and/or archival material was performed. The presence of gene amplification was determined by chromogenic in-situ hybridization. RESULTS. EGFR and HER-2/ neu protein were detected by immunohistochemistry in 21 of 38 (55.3{\%}) and 20 of 38 (52.6{\%}) synovial specimens, respectively. EGFR immunoreactivity showed a granular and membranous pattern, whereas HER-2/ neu immunoreactivity demonstrated only a membrane pattern. Coexpression was observed in 13 of 38 specimens (34.2{\%}). HER-2/ neu expression by immunohistochemistry in synovial sarcomas was restricted to tumors with the SYT/SSX1 translocations. Of 6 specimens with SSX2 translocation, none (0{\%}) showed HER-2/ neu immunoreactivity and 1 (17{\%}) demonstrated EGFR expression. Q-PCR demonstrated the presence of mRNA for EGFR and HER-2/ neu in 19 of 30 specimens (63.3{\%}) and 22 of 30 specimens (73.3{\%}), respectively. EGFR and HER-2/ neu were expressed at low concentrations compared with the expression of glyceraldehyde 3-phosphate dehydrogenase (GAPDH). No evidence of gene amplification was observed. CONCLUSIONS. EGFR and HER-2/ neu are expressed in the majority of patients with SYT/SSX1 synovial sarcomas, albeit at low levels. Treatment with tyrosine kinase inhibitors may represent appropriate alternate therapy for these patients.",
keywords = "Chromogenic in situ hybridization, Epidermal growth factor receptor, HER-2/ neu, Immunohistochemistry, Quantitative polymerase chain reaction, Synovial sarcoma",
author = "Thomas, {Dafydd G.} and Giordano, {Thomas J.} and Donita Sanders and Sybil Biermann and Sondak, {Vernon K.} and Jonathan Trent and Dihua Yu and Pollock, {Raphael E.} and Laurence Baker",
year = "2005",
month = "2",
day = "15",
doi = "10.1002/cncr.20847",
language = "English",
volume = "103",
pages = "830--838",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "4",

}

TY - JOUR

T1 - Expression of receptor tyrosine kinases epidermal growth factor receptor and HER-2/ neu in synovial sarcoma

AU - Thomas, Dafydd G.

AU - Giordano, Thomas J.

AU - Sanders, Donita

AU - Biermann, Sybil

AU - Sondak, Vernon K.

AU - Trent, Jonathan

AU - Yu, Dihua

AU - Pollock, Raphael E.

AU - Baker, Laurence

PY - 2005/2/15

Y1 - 2005/2/15

N2 - BACKGROUND. Synovial sarcomas are high-grade soft tissue neoplasms often characterized by a biphasic spindle and epithelioid cell morphology. The majority of synovial sarcomas harbor a specific chromosomal translocation in which the proximal portion of the SYT gene at chromosome 18q11 is fused to the distal portion of one of several duplicated SSX genes (most notably SSX1 and SSX2) at chromosome Xp11. SYT/SSX1 translocations are seen in nearly three times as many synovial sarcomas as SYT/SSX2 translocations. Although the SYT/SSX2 fusion is usually associated with the monophasic disease pattern, the SYT/SSX1 fusion is present in tumors with biphasic or monophasic patterns. The SYT/SSX1 fusion gene is associated with more aggressive tumor growth and poor outcome. Despite advances in the therapy of local disease, distant metastasis remains the predominant cause of death. Accordingly, there is a need for alternate therapies, such as those recently developed against the receptor tyrosine kinases, such as epidermal growth factor receptor (EGFR) and HER-2/ neu. METHODS. Archival specimens of synovial sarcoma (n = 38) representing 30 patients were assessed for EGFR and HER-2/ neu protein expression by standard immunohistochemical techniques. To validate the immunohistochemistry results, quantitative real-time polymerase chain reaction (Q-PCR) assays using either fresh and/or archival material was performed. The presence of gene amplification was determined by chromogenic in-situ hybridization. RESULTS. EGFR and HER-2/ neu protein were detected by immunohistochemistry in 21 of 38 (55.3%) and 20 of 38 (52.6%) synovial specimens, respectively. EGFR immunoreactivity showed a granular and membranous pattern, whereas HER-2/ neu immunoreactivity demonstrated only a membrane pattern. Coexpression was observed in 13 of 38 specimens (34.2%). HER-2/ neu expression by immunohistochemistry in synovial sarcomas was restricted to tumors with the SYT/SSX1 translocations. Of 6 specimens with SSX2 translocation, none (0%) showed HER-2/ neu immunoreactivity and 1 (17%) demonstrated EGFR expression. Q-PCR demonstrated the presence of mRNA for EGFR and HER-2/ neu in 19 of 30 specimens (63.3%) and 22 of 30 specimens (73.3%), respectively. EGFR and HER-2/ neu were expressed at low concentrations compared with the expression of glyceraldehyde 3-phosphate dehydrogenase (GAPDH). No evidence of gene amplification was observed. CONCLUSIONS. EGFR and HER-2/ neu are expressed in the majority of patients with SYT/SSX1 synovial sarcomas, albeit at low levels. Treatment with tyrosine kinase inhibitors may represent appropriate alternate therapy for these patients.

AB - BACKGROUND. Synovial sarcomas are high-grade soft tissue neoplasms often characterized by a biphasic spindle and epithelioid cell morphology. The majority of synovial sarcomas harbor a specific chromosomal translocation in which the proximal portion of the SYT gene at chromosome 18q11 is fused to the distal portion of one of several duplicated SSX genes (most notably SSX1 and SSX2) at chromosome Xp11. SYT/SSX1 translocations are seen in nearly three times as many synovial sarcomas as SYT/SSX2 translocations. Although the SYT/SSX2 fusion is usually associated with the monophasic disease pattern, the SYT/SSX1 fusion is present in tumors with biphasic or monophasic patterns. The SYT/SSX1 fusion gene is associated with more aggressive tumor growth and poor outcome. Despite advances in the therapy of local disease, distant metastasis remains the predominant cause of death. Accordingly, there is a need for alternate therapies, such as those recently developed against the receptor tyrosine kinases, such as epidermal growth factor receptor (EGFR) and HER-2/ neu. METHODS. Archival specimens of synovial sarcoma (n = 38) representing 30 patients were assessed for EGFR and HER-2/ neu protein expression by standard immunohistochemical techniques. To validate the immunohistochemistry results, quantitative real-time polymerase chain reaction (Q-PCR) assays using either fresh and/or archival material was performed. The presence of gene amplification was determined by chromogenic in-situ hybridization. RESULTS. EGFR and HER-2/ neu protein were detected by immunohistochemistry in 21 of 38 (55.3%) and 20 of 38 (52.6%) synovial specimens, respectively. EGFR immunoreactivity showed a granular and membranous pattern, whereas HER-2/ neu immunoreactivity demonstrated only a membrane pattern. Coexpression was observed in 13 of 38 specimens (34.2%). HER-2/ neu expression by immunohistochemistry in synovial sarcomas was restricted to tumors with the SYT/SSX1 translocations. Of 6 specimens with SSX2 translocation, none (0%) showed HER-2/ neu immunoreactivity and 1 (17%) demonstrated EGFR expression. Q-PCR demonstrated the presence of mRNA for EGFR and HER-2/ neu in 19 of 30 specimens (63.3%) and 22 of 30 specimens (73.3%), respectively. EGFR and HER-2/ neu were expressed at low concentrations compared with the expression of glyceraldehyde 3-phosphate dehydrogenase (GAPDH). No evidence of gene amplification was observed. CONCLUSIONS. EGFR and HER-2/ neu are expressed in the majority of patients with SYT/SSX1 synovial sarcomas, albeit at low levels. Treatment with tyrosine kinase inhibitors may represent appropriate alternate therapy for these patients.

KW - Chromogenic in situ hybridization

KW - Epidermal growth factor receptor

KW - HER-2/ neu

KW - Immunohistochemistry

KW - Quantitative polymerase chain reaction

KW - Synovial sarcoma

UR - http://www.scopus.com/inward/record.url?scp=13444291031&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=13444291031&partnerID=8YFLogxK

U2 - 10.1002/cncr.20847

DO - 10.1002/cncr.20847

M3 - Article

C2 - 15641030

AN - SCOPUS:13444291031

VL - 103

SP - 830

EP - 838

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 4

ER -