Impact of SYT-SSX fusion type on the clinical behavior of synovial sarcoma

A multi-institutional retrospective study of 243 patients

Marc Ladanyi, Cristina R. Antonescu, James M. Woodruff, Denis H. Leung, Akira Kawai, John H. Healey, Murray F. Brennan, Julia Ann Bridge, Julia A. Bridge, Julia A. Bridge, James R. Neff, Frederic G. Barr, Jeffrey D. Goldsmith, John S.J. Brooks, John R. Goldblum, Syed Z. Ali, Janet Shipley, Colin S. Cooper, Cyril Fisher, Björn Skytting & 1 others Olle Larsson

Research output: Contribution to journalArticle

380 Citations (Scopus)

Abstract

Synovial sarcomas are aggressive spindle cell sarcomas containing in some cases areas of epithelial differentiation. They consistently show a specific t(X;18;p11;q11), which usually represents either of two gene fusions, SYT-SSX1 or SYT-SSX2, encoding putative transcriptional proteins differing at 13 amino acid positions. Previous studies have suggested that patients with SYT-SSX2 tumors do better than those with SYT-SSX1 tumors, but the study groups were too limited to be conclusive. To address this issue more definitively, we collected data on SYT-SSX fusion type, pathology, and clinical course in a retrospective multi-institutional study of 243 patients (age range, 6-82) with synovial sarcoma. SYT-SSX1 and SYT-SSX2 fusions were detected in 147 tumors (61%) and 91 tumors (37%), respectively. Histologically, 61 (25%) were classified as biphasic type and 180 (74%) as monophasic type based on the presence or absence of areas of glandular epithelial differentiation, respectively. Median and 5-year overall survivals for the SYT-SSX1 and SYT-SSX2 groups were 6.1 years and 53%, and 13.7 years and 73%, respectively. Overall survival was significantly better among SYT-SSX2 cases (P = 0.03), among cases localized at diagnosis (P < 0.0001), and among patients with primary tumors < 5 cm in greatest dimension (P = 0.01). Age, sex, histological type, and axial versus peripheral primary site had no impact on overall survival. The impact of fusion type on survival remained significant when stratified for primary tumor size (P = 0.03) but was no longer significant when stratified for disease status at presentation. This may reflect the tendency for patients with SYT-SSX1 tumors to present more often with metastatic disease (P = 0.05). Cox regression identified disease status (P < 0.0001) and primary tumor size (P = 0.04) as the only factors independently predictive of overall survival in the subset of 160 patients with information on all of the factors. Within the subset of patients with localized disease at diagnosis (n = 202), the median and 5-year survival for the SYT-SSX1 and the SYT-SSX2 groups were 9.2 years and 61% versus 13.7 years and 77%, respectively. Patients whose tumors contained the SYT-SSX2 fusion (P = 0.08) or were smaller (P = 0.12) showed a trend toward better survival by log-rank test, whereas tumor histology had no impact (P = 0.8). In a Cox regression analysis considering all of the factors, SYT-SSX fusion type emerged as the only independent significant factor (P = 0.04) for overall survival within the subset of 133 patients with localized disease at diagnosis who had information on all of the factors. Among other comparisons, there was a strong association of fusion type and morphology (P < 0.001), with almost all of the SYT-SSX2 tumors showing absence of glandular differentiation (monophasic histology) and almost all of the biphasic tumors containing SYT-SSX1. There was also a statistically significant association of fusion type and patient sex (P = 0.03); specifically, the male:female ration of SYT-SSX1 case was 1:1, whereas for SYT-SSX2 cases, it was close to 1:2. Overall, SYT-SSX fusion type appears to be single most significant prognostic factor by multivariate analysis in patients with localized disease at diagnosis. SYT-SSX fusion type also appears to exert part of its impact on prognosis before presentation through its association with stage at diagnosis. In addition, the association of SYT-SSX fusion type with patient sex and tumor epithelial differentiation point to interesting mechanistic biological differences.

Original languageEnglish (US)
Pages (from-to)135-140
Number of pages6
JournalCancer Research
Volume62
Issue number1
StatePublished - Jan 1 2002

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Synovial Sarcoma
Retrospective Studies
Neoplasms
Survival
SYT-SSX fusion protein
Histology
Clinical Pathology
Gene Fusion

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Ladanyi, M., Antonescu, C. R., Woodruff, J. M., Leung, D. H., Kawai, A., Healey, J. H., ... Larsson, O. (2002). Impact of SYT-SSX fusion type on the clinical behavior of synovial sarcoma: A multi-institutional retrospective study of 243 patients. Cancer Research, 62(1), 135-140.

Impact of SYT-SSX fusion type on the clinical behavior of synovial sarcoma : A multi-institutional retrospective study of 243 patients. / Ladanyi, Marc; Antonescu, Cristina R.; Woodruff, James M.; Leung, Denis H.; Kawai, Akira; Healey, John H.; Brennan, Murray F.; Bridge, Julia Ann; Bridge, Julia A.; Bridge, Julia A.; Neff, James R.; Barr, Frederic G.; Goldsmith, Jeffrey D.; Brooks, John S.J.; Goldblum, John R.; Ali, Syed Z.; Shipley, Janet; Cooper, Colin S.; Fisher, Cyril; Skytting, Björn; Larsson, Olle.

In: Cancer Research, Vol. 62, No. 1, 01.01.2002, p. 135-140.

Research output: Contribution to journalArticle

Ladanyi, M, Antonescu, CR, Woodruff, JM, Leung, DH, Kawai, A, Healey, JH, Brennan, MF, Bridge, JA, Bridge, JA, Bridge, JA, Neff, JR, Barr, FG, Goldsmith, JD, Brooks, JSJ, Goldblum, JR, Ali, SZ, Shipley, J, Cooper, CS, Fisher, C, Skytting, B & Larsson, O 2002, 'Impact of SYT-SSX fusion type on the clinical behavior of synovial sarcoma: A multi-institutional retrospective study of 243 patients', Cancer Research, vol. 62, no. 1, pp. 135-140.
Ladanyi M, Antonescu CR, Woodruff JM, Leung DH, Kawai A, Healey JH et al. Impact of SYT-SSX fusion type on the clinical behavior of synovial sarcoma: A multi-institutional retrospective study of 243 patients. Cancer Research. 2002 Jan 1;62(1):135-140.
Ladanyi, Marc ; Antonescu, Cristina R. ; Woodruff, James M. ; Leung, Denis H. ; Kawai, Akira ; Healey, John H. ; Brennan, Murray F. ; Bridge, Julia Ann ; Bridge, Julia A. ; Bridge, Julia A. ; Neff, James R. ; Barr, Frederic G. ; Goldsmith, Jeffrey D. ; Brooks, John S.J. ; Goldblum, John R. ; Ali, Syed Z. ; Shipley, Janet ; Cooper, Colin S. ; Fisher, Cyril ; Skytting, Björn ; Larsson, Olle. / Impact of SYT-SSX fusion type on the clinical behavior of synovial sarcoma : A multi-institutional retrospective study of 243 patients. In: Cancer Research. 2002 ; Vol. 62, No. 1. pp. 135-140.
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abstract = "Synovial sarcomas are aggressive spindle cell sarcomas containing in some cases areas of epithelial differentiation. They consistently show a specific t(X;18;p11;q11), which usually represents either of two gene fusions, SYT-SSX1 or SYT-SSX2, encoding putative transcriptional proteins differing at 13 amino acid positions. Previous studies have suggested that patients with SYT-SSX2 tumors do better than those with SYT-SSX1 tumors, but the study groups were too limited to be conclusive. To address this issue more definitively, we collected data on SYT-SSX fusion type, pathology, and clinical course in a retrospective multi-institutional study of 243 patients (age range, 6-82) with synovial sarcoma. SYT-SSX1 and SYT-SSX2 fusions were detected in 147 tumors (61{\%}) and 91 tumors (37{\%}), respectively. Histologically, 61 (25{\%}) were classified as biphasic type and 180 (74{\%}) as monophasic type based on the presence or absence of areas of glandular epithelial differentiation, respectively. Median and 5-year overall survivals for the SYT-SSX1 and SYT-SSX2 groups were 6.1 years and 53{\%}, and 13.7 years and 73{\%}, respectively. Overall survival was significantly better among SYT-SSX2 cases (P = 0.03), among cases localized at diagnosis (P < 0.0001), and among patients with primary tumors < 5 cm in greatest dimension (P = 0.01). Age, sex, histological type, and axial versus peripheral primary site had no impact on overall survival. The impact of fusion type on survival remained significant when stratified for primary tumor size (P = 0.03) but was no longer significant when stratified for disease status at presentation. This may reflect the tendency for patients with SYT-SSX1 tumors to present more often with metastatic disease (P = 0.05). Cox regression identified disease status (P < 0.0001) and primary tumor size (P = 0.04) as the only factors independently predictive of overall survival in the subset of 160 patients with information on all of the factors. Within the subset of patients with localized disease at diagnosis (n = 202), the median and 5-year survival for the SYT-SSX1 and the SYT-SSX2 groups were 9.2 years and 61{\%} versus 13.7 years and 77{\%}, respectively. Patients whose tumors contained the SYT-SSX2 fusion (P = 0.08) or were smaller (P = 0.12) showed a trend toward better survival by log-rank test, whereas tumor histology had no impact (P = 0.8). In a Cox regression analysis considering all of the factors, SYT-SSX fusion type emerged as the only independent significant factor (P = 0.04) for overall survival within the subset of 133 patients with localized disease at diagnosis who had information on all of the factors. Among other comparisons, there was a strong association of fusion type and morphology (P < 0.001), with almost all of the SYT-SSX2 tumors showing absence of glandular differentiation (monophasic histology) and almost all of the biphasic tumors containing SYT-SSX1. There was also a statistically significant association of fusion type and patient sex (P = 0.03); specifically, the male:female ration of SYT-SSX1 case was 1:1, whereas for SYT-SSX2 cases, it was close to 1:2. Overall, SYT-SSX fusion type appears to be single most significant prognostic factor by multivariate analysis in patients with localized disease at diagnosis. SYT-SSX fusion type also appears to exert part of its impact on prognosis before presentation through its association with stage at diagnosis. In addition, the association of SYT-SSX fusion type with patient sex and tumor epithelial differentiation point to interesting mechanistic biological differences.",
author = "Marc Ladanyi and Antonescu, {Cristina R.} and Woodruff, {James M.} and Leung, {Denis H.} and Akira Kawai and Healey, {John H.} and Brennan, {Murray F.} and Bridge, {Julia Ann} and Bridge, {Julia A.} and Bridge, {Julia A.} and Neff, {James R.} and Barr, {Frederic G.} and Goldsmith, {Jeffrey D.} and Brooks, {John S.J.} and Goldblum, {John R.} and Ali, {Syed Z.} and Janet Shipley and Cooper, {Colin S.} and Cyril Fisher and Bj{\"o}rn Skytting and Olle Larsson",
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T1 - Impact of SYT-SSX fusion type on the clinical behavior of synovial sarcoma

T2 - A multi-institutional retrospective study of 243 patients

AU - Ladanyi, Marc

AU - Antonescu, Cristina R.

AU - Woodruff, James M.

AU - Leung, Denis H.

AU - Kawai, Akira

AU - Healey, John H.

AU - Brennan, Murray F.

AU - Bridge, Julia Ann

AU - Bridge, Julia A.

AU - Bridge, Julia A.

AU - Neff, James R.

AU - Barr, Frederic G.

AU - Goldsmith, Jeffrey D.

AU - Brooks, John S.J.

AU - Goldblum, John R.

AU - Ali, Syed Z.

AU - Shipley, Janet

AU - Cooper, Colin S.

AU - Fisher, Cyril

AU - Skytting, Björn

AU - Larsson, Olle

PY - 2002/1/1

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N2 - Synovial sarcomas are aggressive spindle cell sarcomas containing in some cases areas of epithelial differentiation. They consistently show a specific t(X;18;p11;q11), which usually represents either of two gene fusions, SYT-SSX1 or SYT-SSX2, encoding putative transcriptional proteins differing at 13 amino acid positions. Previous studies have suggested that patients with SYT-SSX2 tumors do better than those with SYT-SSX1 tumors, but the study groups were too limited to be conclusive. To address this issue more definitively, we collected data on SYT-SSX fusion type, pathology, and clinical course in a retrospective multi-institutional study of 243 patients (age range, 6-82) with synovial sarcoma. SYT-SSX1 and SYT-SSX2 fusions were detected in 147 tumors (61%) and 91 tumors (37%), respectively. Histologically, 61 (25%) were classified as biphasic type and 180 (74%) as monophasic type based on the presence or absence of areas of glandular epithelial differentiation, respectively. Median and 5-year overall survivals for the SYT-SSX1 and SYT-SSX2 groups were 6.1 years and 53%, and 13.7 years and 73%, respectively. Overall survival was significantly better among SYT-SSX2 cases (P = 0.03), among cases localized at diagnosis (P < 0.0001), and among patients with primary tumors < 5 cm in greatest dimension (P = 0.01). Age, sex, histological type, and axial versus peripheral primary site had no impact on overall survival. The impact of fusion type on survival remained significant when stratified for primary tumor size (P = 0.03) but was no longer significant when stratified for disease status at presentation. This may reflect the tendency for patients with SYT-SSX1 tumors to present more often with metastatic disease (P = 0.05). Cox regression identified disease status (P < 0.0001) and primary tumor size (P = 0.04) as the only factors independently predictive of overall survival in the subset of 160 patients with information on all of the factors. Within the subset of patients with localized disease at diagnosis (n = 202), the median and 5-year survival for the SYT-SSX1 and the SYT-SSX2 groups were 9.2 years and 61% versus 13.7 years and 77%, respectively. Patients whose tumors contained the SYT-SSX2 fusion (P = 0.08) or were smaller (P = 0.12) showed a trend toward better survival by log-rank test, whereas tumor histology had no impact (P = 0.8). In a Cox regression analysis considering all of the factors, SYT-SSX fusion type emerged as the only independent significant factor (P = 0.04) for overall survival within the subset of 133 patients with localized disease at diagnosis who had information on all of the factors. Among other comparisons, there was a strong association of fusion type and morphology (P < 0.001), with almost all of the SYT-SSX2 tumors showing absence of glandular differentiation (monophasic histology) and almost all of the biphasic tumors containing SYT-SSX1. There was also a statistically significant association of fusion type and patient sex (P = 0.03); specifically, the male:female ration of SYT-SSX1 case was 1:1, whereas for SYT-SSX2 cases, it was close to 1:2. Overall, SYT-SSX fusion type appears to be single most significant prognostic factor by multivariate analysis in patients with localized disease at diagnosis. SYT-SSX fusion type also appears to exert part of its impact on prognosis before presentation through its association with stage at diagnosis. In addition, the association of SYT-SSX fusion type with patient sex and tumor epithelial differentiation point to interesting mechanistic biological differences.

AB - Synovial sarcomas are aggressive spindle cell sarcomas containing in some cases areas of epithelial differentiation. They consistently show a specific t(X;18;p11;q11), which usually represents either of two gene fusions, SYT-SSX1 or SYT-SSX2, encoding putative transcriptional proteins differing at 13 amino acid positions. Previous studies have suggested that patients with SYT-SSX2 tumors do better than those with SYT-SSX1 tumors, but the study groups were too limited to be conclusive. To address this issue more definitively, we collected data on SYT-SSX fusion type, pathology, and clinical course in a retrospective multi-institutional study of 243 patients (age range, 6-82) with synovial sarcoma. SYT-SSX1 and SYT-SSX2 fusions were detected in 147 tumors (61%) and 91 tumors (37%), respectively. Histologically, 61 (25%) were classified as biphasic type and 180 (74%) as monophasic type based on the presence or absence of areas of glandular epithelial differentiation, respectively. Median and 5-year overall survivals for the SYT-SSX1 and SYT-SSX2 groups were 6.1 years and 53%, and 13.7 years and 73%, respectively. Overall survival was significantly better among SYT-SSX2 cases (P = 0.03), among cases localized at diagnosis (P < 0.0001), and among patients with primary tumors < 5 cm in greatest dimension (P = 0.01). Age, sex, histological type, and axial versus peripheral primary site had no impact on overall survival. The impact of fusion type on survival remained significant when stratified for primary tumor size (P = 0.03) but was no longer significant when stratified for disease status at presentation. This may reflect the tendency for patients with SYT-SSX1 tumors to present more often with metastatic disease (P = 0.05). Cox regression identified disease status (P < 0.0001) and primary tumor size (P = 0.04) as the only factors independently predictive of overall survival in the subset of 160 patients with information on all of the factors. Within the subset of patients with localized disease at diagnosis (n = 202), the median and 5-year survival for the SYT-SSX1 and the SYT-SSX2 groups were 9.2 years and 61% versus 13.7 years and 77%, respectively. Patients whose tumors contained the SYT-SSX2 fusion (P = 0.08) or were smaller (P = 0.12) showed a trend toward better survival by log-rank test, whereas tumor histology had no impact (P = 0.8). In a Cox regression analysis considering all of the factors, SYT-SSX fusion type emerged as the only independent significant factor (P = 0.04) for overall survival within the subset of 133 patients with localized disease at diagnosis who had information on all of the factors. Among other comparisons, there was a strong association of fusion type and morphology (P < 0.001), with almost all of the SYT-SSX2 tumors showing absence of glandular differentiation (monophasic histology) and almost all of the biphasic tumors containing SYT-SSX1. There was also a statistically significant association of fusion type and patient sex (P = 0.03); specifically, the male:female ration of SYT-SSX1 case was 1:1, whereas for SYT-SSX2 cases, it was close to 1:2. Overall, SYT-SSX fusion type appears to be single most significant prognostic factor by multivariate analysis in patients with localized disease at diagnosis. SYT-SSX fusion type also appears to exert part of its impact on prognosis before presentation through its association with stage at diagnosis. In addition, the association of SYT-SSX fusion type with patient sex and tumor epithelial differentiation point to interesting mechanistic biological differences.

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