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Prognostic and predictive role of CXCR4, IGF-1R and Ezrin expression in localized synovial sarcoma: is chemotaxis important to tumor response?

Palmerini E, Benassi MS, Quattrini I, Pazzaglia L, Donati D, Benini S, Gamberi G, Gambarotti M, Picci P, Ferrari S - Orphanet J Rare Dis (2015)

Bottom Line: No survival difference was found according to Ezrin expression.Our findings have important potential implications demonstrating that together with clinical prognostic factors such as radiotherapy and age, CXCR4 and IGF-1R negatively influences survival in patients with localized SS.We believe that further studies addressed to the effects of CXCR4 and IGF-1R inhibitors on cell viability and function are needed to plan new and more appropriate SS treatments.

View Article: PubMed Central - PubMed

ABSTRACT

Background: Synovial sarcoma (SS) is a rare tumor, with dismal survival when metastatic. The role of adjuvant chemotherapy is debated. New prognostic and predictive factors are needed.

Methods: We reviewed patients with localized SS; SS18-SSX fusion transcript presence was confirmed by FISH and RT-PCR. Expression of CXCR4, IGF-1R and Ezrin were evaluated by immunohistochemistry.

Results: Tumor samples from 88 SS patients (45 female; 43 male) with median age 37 years (range 11-63) were selected. The size of the lesion was > 5 cm in 68% of patients and 34% of cases presented biphasic histotype. All patients underwent surgery, 56% adjuvant radiotherapy (RT), 65% adjuvant chemotherapy. A positive stain for IGF-1R was detected in 55 patients, with nucleus expression in 21 patients. CXCR4 was expressed in 74 patients, nuclear pattern in 31 patients. 80 SS were positive to Ezrin, 48 had cytoplasmatic location, 32 membrane location. With a median follow-up of 6 years (1-30 years), the 5-year overall survival (OS) was 70% (95% CI 60-81). 5-year OS was 63% (95% CI 41-85%) for patients with positive IGF-1R/nuclear expression, and 73% (95% CI 61-85%; P = 0.05) in negative patients. 5-year OS was 47% (95% CI 27-66%) in patients with positive CXCR4/nuclear staining, and 86% (95% CI 76-96%, P = 0.0003) in negative cases. No survival difference was found according to Ezrin expression. By multivariate analysis, nuclear expression of CXCR4 and IGF-1R was confirmed independent adverse prognostic factor for SS patient survival linked to the use of chemotherapy.

Conclusions: Our findings have important potential implications demonstrating that together with clinical prognostic factors such as radiotherapy and age, CXCR4 and IGF-1R negatively influences survival in patients with localized SS. We believe that further studies addressed to the effects of CXCR4 and IGF-1R inhibitors on cell viability and function are needed to plan new and more appropriate SS treatments.

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Related in: MedlinePlus

Expression of CXCR4 and IGF-1R in synovial sarcoma. Immunohistochemical expression of CXCR4 with cytoplasmatic (a) and nuclear (b) distribution. Immunohistochemical expression of IGF-1R with cytoplasmatic (c), and nuclear distribution (d) (IHC 20X).
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Fig1: Expression of CXCR4 and IGF-1R in synovial sarcoma. Immunohistochemical expression of CXCR4 with cytoplasmatic (a) and nuclear (b) distribution. Immunohistochemical expression of IGF-1R with cytoplasmatic (c), and nuclear distribution (d) (IHC 20X).

Mentions: CXCR4 was positive in 74 SS (84%), 43 had a membrane/cytoplasmatic staining, 31 nuclear (7 nuclear only and 24 nuclear and cytoplasmatic) (Figure 1a,b).Figure 1


Prognostic and predictive role of CXCR4, IGF-1R and Ezrin expression in localized synovial sarcoma: is chemotaxis important to tumor response?

Palmerini E, Benassi MS, Quattrini I, Pazzaglia L, Donati D, Benini S, Gamberi G, Gambarotti M, Picci P, Ferrari S - Orphanet J Rare Dis (2015)

Expression of CXCR4 and IGF-1R in synovial sarcoma. Immunohistochemical expression of CXCR4 with cytoplasmatic (a) and nuclear (b) distribution. Immunohistochemical expression of IGF-1R with cytoplasmatic (c), and nuclear distribution (d) (IHC 20X).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4320838&req=5

Fig1: Expression of CXCR4 and IGF-1R in synovial sarcoma. Immunohistochemical expression of CXCR4 with cytoplasmatic (a) and nuclear (b) distribution. Immunohistochemical expression of IGF-1R with cytoplasmatic (c), and nuclear distribution (d) (IHC 20X).
Mentions: CXCR4 was positive in 74 SS (84%), 43 had a membrane/cytoplasmatic staining, 31 nuclear (7 nuclear only and 24 nuclear and cytoplasmatic) (Figure 1a,b).Figure 1

Bottom Line: No survival difference was found according to Ezrin expression.Our findings have important potential implications demonstrating that together with clinical prognostic factors such as radiotherapy and age, CXCR4 and IGF-1R negatively influences survival in patients with localized SS.We believe that further studies addressed to the effects of CXCR4 and IGF-1R inhibitors on cell viability and function are needed to plan new and more appropriate SS treatments.

View Article: PubMed Central - PubMed

ABSTRACT

Background: Synovial sarcoma (SS) is a rare tumor, with dismal survival when metastatic. The role of adjuvant chemotherapy is debated. New prognostic and predictive factors are needed.

Methods: We reviewed patients with localized SS; SS18-SSX fusion transcript presence was confirmed by FISH and RT-PCR. Expression of CXCR4, IGF-1R and Ezrin were evaluated by immunohistochemistry.

Results: Tumor samples from 88 SS patients (45 female; 43 male) with median age 37 years (range 11-63) were selected. The size of the lesion was > 5 cm in 68% of patients and 34% of cases presented biphasic histotype. All patients underwent surgery, 56% adjuvant radiotherapy (RT), 65% adjuvant chemotherapy. A positive stain for IGF-1R was detected in 55 patients, with nucleus expression in 21 patients. CXCR4 was expressed in 74 patients, nuclear pattern in 31 patients. 80 SS were positive to Ezrin, 48 had cytoplasmatic location, 32 membrane location. With a median follow-up of 6 years (1-30 years), the 5-year overall survival (OS) was 70% (95% CI 60-81). 5-year OS was 63% (95% CI 41-85%) for patients with positive IGF-1R/nuclear expression, and 73% (95% CI 61-85%; P = 0.05) in negative patients. 5-year OS was 47% (95% CI 27-66%) in patients with positive CXCR4/nuclear staining, and 86% (95% CI 76-96%, P = 0.0003) in negative cases. No survival difference was found according to Ezrin expression. By multivariate analysis, nuclear expression of CXCR4 and IGF-1R was confirmed independent adverse prognostic factor for SS patient survival linked to the use of chemotherapy.

Conclusions: Our findings have important potential implications demonstrating that together with clinical prognostic factors such as radiotherapy and age, CXCR4 and IGF-1R negatively influences survival in patients with localized SS. We believe that further studies addressed to the effects of CXCR4 and IGF-1R inhibitors on cell viability and function are needed to plan new and more appropriate SS treatments.

Show MeSH
Related in: MedlinePlus